This is a woman with abrupt, painless and severe loss (she only sees the movement of the hands) of vision in one eye. She does not give us much information from the ocular examination, only that there is an afferent pupillary defect. We have to rely on systemic symptoms to diagnose the problem. This is an elderly woman with typical symptoms of polymyalgia rheumatica, and the pain in the temporomandibular region is very suggestive. It is giant cell arteritis or temporal arteritis. The most common ocular manifestation is anterior ischemic optic neuropathy. In the fundus we would certainly see a papillary edema of that eye, with a gypsum white coloration. The afferent pupillary defect is very characteristic of these severe ischemic optic neuropathies. Suspecting giant cell arteritis, there are three analytical markers that are characteristically high: CRP, ESR and platelet count. We will first request one of these parameters and treat it often without waiting for biopsy confirmation. Therefore, option 2 is the correct one.

This is a woman with abrupt, painless and severe loss (she only sees the movement of the hands) of vision in one eye. She does not give us much information from the ocular examination, only that there is an afferent pupillary defect. We have to rely on systemic symptoms to diagnose the problem. This is an elderly woman with typical symptoms of polymyalgia rheumatica, and the pain in the temporomandibular region is very suggestive. It is giant cell arteritis or temporal arteritis. The most common ocular manifestation is anterior ischemic optic neuropathy. In the fundus we would certainly see a papillary edema of that eye, with a gypsum white coloration. The afferent pupillary defect is very characteristic of these severe ischemic optic neuropathies. Suspecting giant cell arteritis, there are three analytical markers that are characteristically high: CRP, ESR and platelet count. We will first request one of these parameters and treat it often without waiting for biopsy confirmation. Therefore, [HIDDEN].

A 70-year-old woman with a history of anorexia, weight loss, discomfort in the musculature and proximal joints plus pain in the temporomandibular region who comes to the emergency department for unilateral loss of vision (hand movement), sudden and painless onset (afferent pupillary defect). What test would you request first for diagnostic purposes?

Rapid, painless unilateral vision loss in a 37-year-old healthy woman.

A 37-year-old woman experienced painless, progressive vision loss to no light perception in the left eye over the course of 3 days. The right eye was unaffected. On examination, the only other abnormal finding was a +4 left afferent pupillary defect. She was initially diagnosed with retrobulbar optic neuritis and admitted for treatment with intravenous methylprednisolone. Neuro-imaging revealed a large right anterior cerebral artery aneurysm that crossed the midline to compress the left optic nerve. The aneurysm was treated with coil embolization, which was technically successful but which did not lead to significant improvement in vision.

Sudden-onset unilateral painless vision loss.

A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.

InternalMed_Harrison

A careful neurologic examination is an essential first step in the evaluation. In most cases, patients with an abnormal examination or a history of recent-onset headache should be evaluated by a computed tomography (CT) or magnetic resonance imaging (MRI) study. As an initial screening procedure for intracranial pathology in this setting, CT and MRI methods appear to be equally sensitive. In some circumstances, a lumbar puncture (LP) is also required, unless a benign etiology can be otherwise established. A general evaluation of acute headache might include cranial arteries by palpation; cervical spine by Pain induced by bending, lifting, cough Pain associated with local tenderness, e.g., region of temporal artery the effect of passive movement of the head and by imaging; the investigation of cardiovascular and renal status by blood pressure monitoring and urine examination; and eyes by funduscopy, intraocular pressure measurement, and refraction.

Acute visual loss

Giant cell arteritis Giant cell arteritis should be considered in an older person with jaw claudication, temporal pain, and tiredness. Placing the person on steroids might save both their vision and decrease their risk of stroke. Without treatment a person can quickly go blind in both eyes. Vascular occlusions Central retinal artery occlusion: CRAO is characterized by painless, acute vision loss in one eye. Central retinal vein occlusion: CRVO causes sudden, painless vision loss that can be mild to severe. Branch retinal vein occlusion: sudden painless vision loss or visual field defect are the main symptom of BRVO. Branch retinal artery occlusion: BRAO may also cause acute painless loss of vision. Vitreous hemorrhage It is one of the most common causes of acute or subacute decrease in vision. Hyphema Blood in the anterior chamber of the eye is known as hyphema. Severe hyphema covering pupillary area can cause sudden decrease in vision. References Blindness

Recurrent painful ophthalmoplegic neuropathy

Magnetic resonance angiography (MRA) or CT angiography (CTA) can be used to examine cerebral blood vessels and to rule out vascular abnormalities, such as an aneurysm. In cases where intracranial vascular lesions, for example, subarachnoid hemorrhage cannot be completely ruled out after performing MRA or CTA, physicians may consider using traditional digital subtraction angiography (DSA) for more detailed investigation. Laboratory tests Lumbar punctures and blood tests might be performed on those with RPON to identify other possible causes of cranial neuropathy, including diabetes, inflammatory diseases, infections, tumors, and other systemic diseases that involve either the central nervous system or the peripheral nervous system. The detection of abnormalities in these tests suggests that RPON is highly unlikely to be the culprit in cranial neuropathy, and more diagnostic tests should be done to find out the underlying condition.

Atypical retinal vaso-occlusion with structural and functional resolution.

The purpose is to report a patient with primary open-angle glaucoma that developed sudden painless unilateral vision loss, a sequential ophthalmoscopic appearance with features of both central retinal artery and later central retinal vein occlusion, and objective visual system dysfunction in the form of a relative afferent pupil defect, who spontaneously recovered vision along with complete resolution of the pupillary defect over several weeks. A 50-year-old woman with a long-standing history of glaucoma presented with acute, painless vision loss in one eye, a pallid retina with a cherry red macula, diffuse retinal hemorrhages, and a relative afferent pupil defect. Spectral domain optical coherence tomography and fluorescein angiography were essentially normal with neither retinal edema nor retinal ischemia to account for the visual dysfunction. Over the course of 2 months, the patient regained vision and the relative afferent pupil defect, typically a permanent manifestation of retinal destruction, resolved. Not all retinal vaso-occlusive phenomena can be completely attributed to a central retinal vein or artery occlusion. In the patient presented, there was no objective diagnostic testing that revealed a cause for the patient's vision loss or relative afferent pupillary defect. This combined with the complete recovery of vision and resolution of the relative afferent pupillary defect underscores a lack of comprehensive understanding of retinal vaso-occlusive disease.

[Temporal arteritis presenting with headache and abducens nerve palsy. Report of a case].

A 71-year-old man visited our clinic with a 3-day history of severe throbbing headache and 1-day history of horizontal diplopia. He had had jaw claudication and pain in the neck and shoulder several days previously. His right eye was slightly esotropic and did not move laterally. There was no blepharoptosis, proptosis, lid edema, or conjunctival injection. The pupils were unremarkable. The remainder of the cranial nerve functions was intact. There was no limb weakness or sensory impairment. Superficial temporal arteries were swollen and tender on both sides. Laboratory examination showed elevated CRP level and high erythrocyte sedimentation rate. Cranial MR images were unremarkable. The cerebrospinal fluid was acellular with 45 mg/dl of protein. A diagnosis of temporal arteritis was made. Treatment with 50 mg of prednisolone brought about prompt disappearance of the headache. Right ocular movement fully recovered in 10 days. Temporal artery biopsy findings and response to corticosteroid were consistent with temporal arteritis. The motility pattern of the right eye was consistent with complete abducens nerve palsy, which is a rare manifestation of temporal arteritis. Although temporal arteritis is a rare cause of ophthalmoplegia in the elderly patients, swift diagnosis and treatment is necessary to avoid blindness.

Headache

One recommended diagnostic approach is as follows. If any urgent red flags are present such as visual loss, new seizures, new weakness, new confusion, further workup with imaging and possibly a lumbar puncture should be done (see red flags section for more details). If the headache is sudden onset (thunderclap headache), a computed tomography test to look for a brain bleed (subarachnoid hemorrhage) should be done. If the CT scan does not show a bleed, a lumbar puncture should be done to look for blood in the CSF, as the CT scan can be falsely negative and subarachnoid hemorrhages can be fatal. If there are signs of infection such as fever, rash, or stiff neck, a lumbar puncture to look for meningitis should be considered. If there is jaw claudication and scalp tenderness in an older person, a temporal artery biopsy to look for temporal arteritis should be performed and immediate treatment should be started. Neuroimaging

Atypical Leber hereditary optic neuropathy with a 34-year interval between vision loss in both eyes.

Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial disease characterized by painless vision loss affecting both eyes. The disease usually develops in both eyes within weeks to months of onset. We report a case of LHON who presented with unilateral vision loss in childhood with an interval of more than 30 years between vision loss in the two eyes. A 43-year-old man presented with a 1-month history of vision loss in his right eye. At 9 years of age, his visual acuity in the left eye declined, and he had been treated with glaucoma eyedrops bilaterally at his eye clinic. At his first visit to our hospital, his BCVA was 0.15 in the right eye and 0.1 in the left eye, and critical flicker frequency was 16 Hz in the right eye and 15 Hz in the left eye, and he was negative for a relative afferent pupillary defect. The Goldman visual field showed central scotoma in both eyes. Fundus examination revealed slight redness of the right optic disc with meandering retinal small vessels, and the left optic disc had a slight pallor. Fluorescein angiography could not be performed because of liver dysfunction. OCT showed prominent bilateral thinning of the RNFL and retinal ganglion cell layer. Enhancement of the optic nerve was not apparent on orbital gadolinium-enhanced magnetic resonance imaging. Hematologic analysis revealed macrocytic anemia and low levels of vitamin B12 and folate. His mother had a presumptive diagnosis of LHON but did not receive genetic testing. A male cousin also had severe vision loss. Based on the likely family history of LHON, we performed genetic testing, which revealed the 11778 mitochondrial point mutation associated with this condition. We report a case of LHON with 34 years interval in vision loss in the fellow eye. LHON may develop in the second eye decades after its onset in the first. Detailed medical interviews and scrutiny, such as examination of family history, are warranted in consideration of LHON.

First_Aid_Step2

If a 20-year-old female develops headaches after drinking red wine, think migraine. Associated symptoms/signs: Significant findings include fever or rash (consider meningitis or other infectious causes), jaw claudication (specific for temporal arteritis), or constitutional symptoms such as weight loss (associated with neoplastic, inﬂammatory, or infectious conditions). Photophobia, nausea, and vomiting are associated with migraine, aneurysmal SAH, and meningitis, but neck stiffness is more likely to accompany the latter two. Neurologic sequelae: Look for diplopia, mental status changes or associated symptoms (numbness, weakness, dizziness, ataxia, visual disturbances), papilledema, or pupillary abnormalities (partial CN III palsy or Horner’s syndrome). Patient risk factors: High-risk patients are > 50 years of age, immunocompromised, or with preexisting malignancy. If SAH is suspected, obtain a head CT without contrast. If CT is , LP is mandatory. Obtain a CBC.

Ultrasound-Assisted Diagnosis of Optic Neuritis in the Emergency Department: A Case Report.

Optic neuritis is a common cause of subacute unilateral vision loss, occurring in 1-5 per 100,000 persons per year. It is more common in Caucasians, women, and those from countries with northern latitudes. Those aged 20-49 years are at greatest risk. The condition arises due to inflammation of the optic nerve. Inflammation may occur due to systemic inflammatory disorders, most commonly multiple sclerosis. A 21-year-old African-American male presented to our emergency department with a complaint of painful unilateral vision loss. On examination he was found to have a relative afferent pupillary defect and red desaturation. A bedside ultrasound suggested pseudopapilledema suggestive of optic neuritis. He was admitted to Neurology for confirmation of and treatment for optic neuritis. Magnetic resonance imaging confirmed optic neuritis. The patient was treated with i.v. steroids and discharged after improvement in visual function. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Optic neuritis is a clinical diagnosis. The subtle historical components and examination findings make it a diagnostic challenge for the busy emergency physician. Early diagnosis may improve visual outcomes. Discovery of pseudopapilledema on bedside ultrasound may be seen in optic neuritis, and is another finding that emergency physicians may assess for in patient presenting with unilateral vision loss.

[A 62-year-old man with an acute onset of consciousness disturbances].

We report a 62-year-old man who developed coma and died in a fulminant course. The patient was well until May 1, 1996 when he noted chillness, tenderness in his shoulders, and he went to bed without having his lunch and dinner. In the early morning of May 2, his families found him unresponsive and snoring; he was brought into the ER of our hospital. He had histories of hypertension, gout, and hyperlipidemia since 42 years of the age. On admission, his blood pressure was 120/70, heart rate 102 and regular, and body temperature 36.3 degrees C. His respiration was regular and he was not cyanotic. Low pitch rhonchi was heard in his right lower lung field. Otherwise general physical examination was unremarkable. Neurologic examination revealed that he was somnolent and he was only able to respond to simple questions such as opening eyes and grasping the examiner's hand, but he was unable to respond verbally. The optic discs were flat; the right pupil was slightly larger than the left, but both reacted to light. He showed ptosis on the left side, conjugate deviation of eyes to the left, and right facial paresis. The oculocephalic response and the corneal reflex were present. His right extremities were paralyzed and did not respond to pain Deep tendon reflexes were exaggerated on the right side and the plantar response was extensor on the right. No meningeal signs were present. Laboratory examination revealed the following abnormalities; WBC 18,400/ml, GOT 131 IU/l GPT 50 IU/l, CK616 IU/l, BUN 30 mg/dl, Cr 2.1 mg/ dl, glucose 339 mg/dl, and CRP 27.4 mg/dl. ECG showed sinus tachycardia and ST elevation in II, III and a VF leads and abnormal q waves in I, V5, and V6 leads. Chest X-ray revealed cardiac enlargement but the lung fields were clear. Cranial CT scan revealed low density areas in the left middle cerebral and left posterior cerebral artery territories. The patient was treated with intravenous glycerol infusion and other supportive measures. At 2: 10 AM on May 3, he developed sudden hypotension and cardiopulmonary arrest. He was pronounced dead at 3:45 AM. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had acute myocardial infarction involving the inferior and the true posterior walls and left internal carotid embolism from a mural thrombus. Post mortem examination revealed occlusion of the circumflex branch of the left coronary artery due to atherom plaque rupture and myocardial infarction involving the posterior and the lateral wall with a rupture in the postero-lateral wall. Marked atheromatous changes were seen in the left internal carotid, the middle cerebral and the basilar arteries; the left internal carotid and the middle cerebral arteries were almost occluded by thrombi and blood coagulate. The territories of the left middle cerebral and the occipital arteries were infarcted; but the left thalamic area was spared. The neuropathologist concluded that the infarction was thrombotic origin not an embolic one as the atherosclerotic changes were severe. Cardiac rupture appeared to be the cause of terminal sudden hypotension and cardiopulmonary arrest. It appears likely that a vegetation which had been attached to the aortic valve induced thromboembolic occlusion of the left internal carotid artery which had already been markedly sclerotic by atherosclerosis. It is also possible that the vegetations in the aortic valve came from mural thrombi at the site of acute myocardial infarction, as no bacteria were found in those vegetations.

Paracentral Acute Middle Maculopathy After COVID-19 Disease: Multimodal Evaluation.

To report the case and multimodal imaging findings of a healthy young woman who developed paracentral acute middle maculopathy (PAMM) 9 weeks after COVID-19 disease. Case report. Ultra-widefield fundus photography, macular spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and OCT-angiography (OCT-A) were performed. A 36-year-old woman who developed PAMM 9 weeks after SARS-CoV-2 infection. A 36-year-old woman went to the emergency department (ED) with sudden, painless, left eye (LE) vision loss. The only relevant past medical history was COVID-19 disease 9 weeks before. Best corrected visual acuity (BCVA) was 20/200, a LE relative afferent pupillary defect (RAPD) was present and superficial hemorrhages throughout the macular area and peripheral retina were found. Nearly four hours after admission, LE BCVA recovered to 20/20 without RAPD. Five days after presentation in the ED, the patient returned with recurrent LE vision loss, with spontaneous recovery within 12 hours. Macular SD-OCT revealed hyperreflectivity of the inner plexiform and inner nuclear layers and the diagnosis of PAMM was established. The patient started oral acetylsalicylic acid and oral prednisolone. The patient did not report any new episodes of vision loss and there was a progressive resolution of abnormal fundus findings. SARS-CoV-2 infection increases the risk of vascular thrombotic events with possible involvement of the retinal circulation, and PAMM may present as a possible complication. Ophthalmologists should be able to recognize it promptly through multimodal imaging findings.

Anterior ischemic optic neuropathy due to giant cell arteritis with normal inflammatory markers.

In anterior ischemic optic neuropathy (AION), it is important not to miss the diagnosis of giant cell arteritis (GCA) because this requires immediate steroid treatment to prevent involvement of the second eye and possible blindness. A missed diagnosis also might lead to fatal systemic complications. Observational case report. A 79-year-old woman noticed decreased visual and visual field loss in the right eye. At presentation, right visual acuity was 10/20 (ETDRS chart 2000). There was a right relative afferent pupillary defect of 0.6 log units. Asked for symptoms of GCA she complained about temporal and occipital headache, jaw claudication combined with malaise, and myalgia of the upper limbs. Laboratory tests showed normal inflammatory markers. Repeated tests confirmed ESR and CRP to be within the normal range. GCA being suspected, ultrasound of the superficial temporal arteries and temporal artery biopsy were performed unilaterally on the right side. Histology showed a chronic inflammatory cell infiltrate consistent with active GCA. The patient was treated with high-dose corticosteroids (250 mg methylprednisolone, three times/day, initially) and symptoms rapidly resolved, but visual loss remained unchanged. The case presented here proves that GCA with typical related visual loss (AION) is possible even when both ESR and CRP are in the normal range. Therefore, in the presence of typical symptoms, the clinician must not rely solely on laboratory testing, but start steroid therapy immediately and order a temporal artery biopsy.

Sciatica

Cancer should be suspected if there is previous history of it, unexplained weight loss, or unremitting pain. Spinal epidural abscess is more common among those with diabetes mellitus or immunocompromised or who had spinal surgery, injection or catheter; it typically causes fever, leukocytosis and increased erythrocyte sedimentation rate. If cancer or spinal epidural abscess are suspected, urgent magnetic resonance imaging is recommended for confirmation. Proximal diabetic neuropathy typically affects middle aged and older people with well-controlled type-2 diabetes mellitus; onset is sudden causing pain usually in multiple dermatomes quickly followed by weakness. Diagnosis typically involves electromyography and lumbar puncture. Shingles is more common among the elderly and immunocompromised; usually (but not always) pain is followed by appearance of a rash with small blisters along a single dermatome. Acute Lyme radiculopathy may follow a history of outdoor activities during warmer

Lessons of the month 4: Giant cell arteritis with normal inflammatory markers and isolated oculomotor nerve palsy.

Giant cell arteritis (GCA) is an important condition to suspect and treat early, as failure to do so can result in anterior ischaemic optic neuropathy and subsequent permanent visual loss.A 71-year-old woman presented to her local emergency department with a 1-week history of constant, moderate-severe global headache associated with intermittent periorbital pain. Two weeks later she developed sudden horizontal diplopia. Examination demonstrated right oculomotor nerve palsy. Her erythrocyte sedimentation rate (ESR) was 9 mm/hr. Repeat blood tests 1 month later showed an ESR of 67 mm/hr. Temporal artery biopsy was positive.A review from a cohort of 764 patients with suspected GCA who underwent biopsy found the sensitivity of an elevated ESR and c-reactive protein was 84% and 86%, respectively, but the specificity was only 30%. Therefore, inflammatory markers should only act as a guide, and caution should be taken in their interpretation especially with respect to the time of sampling in the disease evolution.Isolated oculomotor nerve palsy in association with GCA is rare. The first case series was described by miller fisher in 1959 who observed two patients presenting with diplopia, ptosis and ocular palsies. In anyone over the age of 50 who develops a new, refractory headache and cranial neuropathy, GCA should be the first consideration.

A tearfully painful darkness.

A 70-year-old woman presented with new onset of left eye and facial pain. Ophthalmic and neurological examinations, magnetic resonance imaging brain, erythrocyte sedimentation rate, and C-reactive protein were unrevealing. A few days later, she developed vision loss in her left eye. Examination revealed decreased visual acuity with a relative afferent pupillary defect in the left eye and a diffuse mild swelling of the left optic nerve head. Repeat magnetic resonance imaging showed T2 hyperintensity and enhancement of the intraorbital optic nerve and surrounding tissues with no other intracranial abnormalities. Serum studies showed elevated myelin oligodendrocyte glycoprotein IgG titer. She was treated with IV methylprednisolone 1000 mg daily for 3 days and was discharged on prolonged prednisone taper with return of vision to baseline.

Lessons to be learned: a case study approach--a case of temporal arteritis.

A 71-year-old male presented with a history of sudden partial visual loss in the right eye with an inferior visual field defect over the past 3-4 days. He had no history of headache or of facial pain. Clinical examination confirmed that vision on the right side was reduced to 6/18 and on the left to 6/12. The right eye showed a relative afferent pupillary defect. There was no other abnormality of the anterior segment of either eye. The right retina showed a pale swollen optic disc and a provisional diagnosis of anterior ischaemic optic neuropathy (AION) was made. An urgent erythrocyte sedimentation rate (ESR) was ordered and the patient was asked to return to the eye clinic in one month. However, 16 days later--when it was first recognised that his ESR was elevated to 75 mm in the first hour--the patient was recalled immediately in order to commence systemic steroid treatment; but regrettably, by this time, his right eye had become totally blind. In this case, although the attending doctor made a correct clinical diagnosis on presentation, he failed to act upon the result of the blood test.

Childhood-Onset Leber Hereditary Optic Neuropathy: Particular Features.

Leber hereditary optic neuropathy (LHON) is an optic neuropathy of mitochondrial inheritance. Childhood-onset disease is relatively rare and there are limited data on this important patient subgroup. We present 3 particular presentations of LHON. Patient 1 was an 8-year-old boy admitted to the emergency department reporting a progressive bilateral visual loss and intermittent headaches. Neuro-ophthalmological examination revealed a bilateral pseudopapilledema. Lumbar puncture identified intracranial hypertension and the brain and orbits magnetic resonance imaging showed T2 hyperintensity in the posterior region of the left optic nerve and the optic chiasm. Patient 2 was a 12-year-old boy admitted to the emergency department reporting painless, progressive central vision loss in the right eye. Fundus examination revealed a hyperemic disc and vascular network papillary and peripapillary vascular microdilations. Three months later, the left eye presented visual loss. Patient 3 was a 6-year-old female child referred to the neuro-ophthalmology specialist due to painless central visual loss in both eyes. Her BCVA was 1/10 and counting fingers in right and left eye, respectively, and fundus examination revealed a pallor optic disc in the temporal sector. The phenotype of childhood-onset disease may present itself distinct from classical adult-onset LHON. The absence of classical clinical features could lead to initial misdiagnosis. There should exist a high index of suspicion in children presenting unexplained subnormal vision in order to avoid potential diagnostic delays.

Masticatory muscle pain: an important indicator of giant cell arteritis.

Giant cell arteritis (GCA) is a polysymptomatic disease which constitutes an ophthalmic emergency because early recognition and management can prevent blindness. There is conflicting information in the literature on the validity, sensitivity, and specificity of various systemic symptoms and signs of GCA. This paper presents a review of our prospective studies on the subject, and our findings are particularly relevant to dentists. We investigated 363 patients in a prospective study. Positive temporal artery biopsy was seen in 106 patients and negative in 257 referred for diagnosis of GCA. Systemic symptoms and signs of GCA and erythrocyte sedimentation rate (Westergren-ESR) and C-reactive protein (CRP) levels were compared in these two groups of patients. The odds of having a positive temporal artery biopsy (i.e., GCA) were 9.1 times greater with jaw claudication (pain in masticatory muscles on eating), 3.4 times with neck pain, 3.2 times with CRP > 2.45 mg/dL, 2.0 times with ESR 47.107 mm/hr, 2.7 times with ESR > 107 mm/hr, and 2.0 times when the patients were aged > or = 75 years. Other signs and symptoms did not show a significant association with a positive biopsy. Our study showed that "normal" ESR values do not rule out GCA but that CRP is a more useful test than ESR. Since jaw claudication is one of the most important symptoms of GCA, dentists should keep this possibility in mind when older patients come complaining of jaw pain while eating.

Posterior ischemic optic neuropathy

Defective light perception in one eye causes an asymmetrical pupillary constriction reflex called the afferent pupillary defect (APD). Arteritic PION A-PION most commonly affects Caucasian women, with an average age of 73. At onset vision loss is unilateral, but without treatment it rapidly progresses to involve both eyes. Vision loss is usually severe, ranging from counting fingers to no light perception. Associated symptoms are jaw pain exacerbated by chewing, scalp tenderness, shoulder and hip pain, headache and fatigue. Perioperative PION Vision loss is usually apparent upon waking from general anesthesia. Signs observable to a bystander include long surgery duration and facial swelling. Vision loss is usually bilateral and severe, ranging from counting fingers to no light perception. Cause

[Transient trochlear nerve palsy as the presenting neurological sign of panarteritis nodosa].

Panarteritis nodosa (PAN) is a systemic vasculitis affecting small and medium-sized arteries. Neuro-ophthalmological complications of PAN are rare but numerous, and may affect the eye, the visual and the oculomotor pathways. Such complications occur mainly in patients previously diagnosed with PAN. A 51-year-old woman presented with an isolated right trochlear (IV) palsy, in the setting of headaches and fluctuating fever of unknown etiology. Erythrocyte sedimentation rate was 13 mm and full blood cell count was normal. Previous chest X-ray and blood studies were negative for an infection or inflammation. Orbital and cerebral CT scan was normal. Spontaneous recovery of diplopia ensued over four days. Two days later, paresthesia and sensory paresis of the dorsal portion of the left foot were present. Lumbar puncture revealed 14 leucocytes (76 percent lymphocytes) with elevated proteins, but blood studies and serologies were negative. A diagnosis of undetermined meningo-myelo-radiculoneuritis was made. Because of a possible tick bite six weeks previously the patient was empirically treated with 2 g intravenous ceftriaxone for 3 weeks. Fever rapidly dropped. Six weeks after the onset of diplopia, acute onset of blindness in her right eye, diffuse arthralgias and fever motivated a new hospitalization. There was a central retinal artery occlusion of the right eye. Blood studies now revealed signs of systemic inflammation (ESR 30 mm, CRP 12 mg/L, ANA 1/80, pANCA 1/40, leucocytosis 12.4 G/L, Hb 111 g/L, Ht 33 percent). Biopsy of the left sural nerve revealed arterial fibrinoid necrosis. A diagnosis of PAN was made. Transient diplopia can be the heralding symptom of a systemic vasculitis such as PAN, giant cell arteritis and Wegener granulomatosis. In this patient the presence of accompanying systemic symptoms raised a suspicion of systemic inflammation, but the absence of serologic and imaging abnormalities precluded a specific diagnosis initially. A few weeks later, the presence of a second ischemic event (retinal) and positive blood studies led to a further diagnostic procedure. Oculomotor and abducens palsies have rarely been reported in association with PAN. We report the first case of trochlear nerve paresis as the inaugural neurological sign of PAN. This case highlights the importance of considering inflammatory systemic disorders in patients with acute diplopia particularly when they are young, lack vascular risk factors or cause, and complain of associated systemic symptoms.

Ankylosing spondylitis

These diagnostic criteria include: Inflammatory back pain:Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up) Past history of inflammation in the joints, heels, or tendon-bone attachments Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions Positive for the biomarker HLA-B27 Good response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) Signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate) Manifestation of psoriasis, inflammatory bowel disease, or inflammation of the eye (uveitis) If these criteria still do not give a compelling diagnosis magnetic resonance imaging (MRI) may be useful. MRI can show inflammation of the sacroiliac joint. Imaging

[Blindness in both eyes due to late diagnosis of giant cell arteritis].

Giant cell arteritis (GCA) is often diagnosed very late, variable "facets" of the disease exist render the diagnosis more difficult. Follow-up observations of five very old patients are reported in whom diagnosis was made too late, resulting in blindness of both eyes. Five patients (age 76-84 years, 4 women, one man) with GCA became blind in both eyes because diagnosis had been delayed (two patients) or onset of therapy was too late (three patients). In two patients who also had arterial hypertension, the symptom "headache" had been misleading. Symptoms of accompanying general diseases masked the real diagnosis, particularly in the second patient who had renal insufficiency, coronary artery disease, and unilateral obstruction of the internal carotid artery. Symptoms that failed to lead to the correct diagnosis were: muscle or chewing pain (three patients), circumscribed numbness around the mouth (second patient), and persistent headache despite normalization of blood pressure. Normal findings from cranial CTAs (two patients) led to the wrong reassurance of the patient. Swelling of the optic disk (two patients) was misdiagnosed by ophthalmologists, as was a retinal branch arterial occlusion (first patient). Three patients, afraid of possible side effects caused by glucocorticoids, took ineffective alternative medications. Poor vigilance led to blindness of the fifth patient with long-standing polymyalgia rheumatica. Targeted examinations at the onset of symptoms are necessary. GCA-symptoms were mis-constructed by additional diseases that disguised the correct diagnosis. The danger of bilateral blindness is particularly great in patients of great age.

Leber's hereditary optic neuropathy following unilateral painful optic neuritis: a case report.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

An Unusual Case of Giant Cell Arteritis.

Giant cell arteritis (GCA), also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. It is the most common vasculitis affecting adults older than 50, with an incidence of 20/100,000 and an average age of onset of 70. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Our patient is a 73-year-old male who presented to the emergency room with 10 days of bilateral headache radiating to the occipital area associated with fevers, persistent chills, generalized weakness, and a headache described as constant, dull, 9 out of 10 pain, and minor pain with neck flexion. Lab work revealed an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The patient had tender palpation to his temples and due to a high suspicion of giant cell arteritis, he was started on high-dose steroids with rapid relief of his symptoms. Biopsy showed evidence of active non-granulomatous vasculitis and confirmed bilateral temporal arteritis within the context of the clinical setting. GCA patients are more likely to be women and typically present with unilateral headache (66% of GCA), jaw claudication (50%), fevers (50%), and transient visual loss (16-54%). Here, we describe a 73-year-old male with a past medical history of cerebral vascular accident (CVA), diabetes, and cancer that presented with 10 days of bilateral headaches and fevers. Unlike the usual presentation, our patient denied any vision and joint pain changes, and the temporal arteries were not stiff to palpation. This patient presentation is unique to previous reports in the limited display of symptoms and absence of the most commonly associated manifestations. Although his presentation supported GCA, the features of elevated ESR and CRP, headache, and fever were too general to diagnose GCA exclusively, and his additional symptoms of rhinorrhea and sinus pain more likely supported infection. Our case indicates the importance of maintaining a high index of clinical suspicion for GCA in the elderly population presenting with headaches and elevated ESR and CRP. GCA, also known as temporal arteritis (TA), is a systemic autoimmune inflammation of medium and large arteries. Typically, patients initially present with new-onset headaches, visual changes and disturbances, jaw claudication, arthralgias, and tender or swollen temporal or occipital arteries. Diagnosis requires high clinical suspicion, and treatment revolves around high doses of steroids.

Three presentations of monocular vision loss.

Carotid artery disease is estimated to affect 30% of persons older than 50. Risk factors include hypertension, cigarette smoking, hyperlipidemia and diabetes mellitus. Symptoms ascribed to carotid artery lesions with stenosis of the artery or plaque formation include monocular vision loss and transient ischemic attacks. Patients can present with transient monocular vision loss as their initial symptom. Three patients from a geriatric clinic in Wilmington, Delaware presented with different complaints of vision loss with similar overall outcomes. Patient A was an 87-year-old woman who presented with dimming of vision on extreme left head turn. Dilated fundus examination found a retinal arterial emboli in the left eye (O.S.). Carotid duplex examination found 50% to 79% left internal carotid stenosis with no hemodynamic stenosis of the right internal carotid. Patient B was a 78-year-old woman who presented with a right superior altitudinal defect and transient vision loss in the right eye. Dilated fundus examination found retinal arterial emboli in the right eye (O.D.). Carotid duplex examination found 50% to 79% carotid stenosis in both the left and right internal carotids. Patient C was an 84-year-old man who complained of a superior altitudinal visual field defect O.D. Dilated fundus examination found a retinal arterial emboli O.D. Carotid duplex results showed calcified atherosclerotic plaques present at the level of the common carotid artery bifurcations bilaterally, with 50% to 70% narrowing of the right internal carotid artery with no significant narrowing of the left internal carotid artery. These 3 presentations show that in patients older than 50 who present with chief complaints of monocular vision loss, a differential diagnosis of carotid artery disease must be considered. Patients who exhibit retinal arterial emboli are at increased risk for stroke and vascular death. Appropriate measures for confirming a diagnosis include duplex ultrasound imaging, magnetic resonance angiography (MRA), and carotid angiography. Surgical techniques such as carotid angioplasty and carotid endarterectomy may be recommended.

[Arteriitis temporalis--a major disease developing in advance age (author's transl)].

Arteriitis temporalis, a disease that was largely unknown in the early fifties, has gained importance in recent years. In the past ten years 32 patients suffering from arteriitis temporalis were diagnosed and treated both in the eye hospital and in the rheumatic-cardiological hospital of the Berlin-Buch Municipal Hospital. The following clinical findings were essential for the diagnosis: advanced or old age of the patient, massive headache in the temporal and/or occipital regions, myalgia primarily in the shoulders and the neck that responded relatively poorly to treatment, reduced eyesight, loss of weight and decrease in vitality. Extremely high BSR, an increased amount of alpha-2 and an increased level of alkaline phosphatase were most important among the laboratory findings. Corticosteroids have proved to be the medicine of choice for treating this condition.

Central retinal artery occlusion as initial presentation of Moyamoya disease in a middle-aged woman.

To present a case of central retinal artery occlusion as the first symptomatic manifestation of Moyamoya disease in a middle-aged patient. Case report of a 48-year-old female Chinese-American patient who presented with sudden onset painless unilateral vision loss. Fundus photos, optical coherence tomography, fluorescein angiography, magnetic resonance angiography, computed tomography angiography, and catheter cerebral angiogram were performed. The patient's dilated fundus examination showed classic findings of a central retinal artery occlusion. Diagnostic brain imaging demonstrated extensive stenosis of the cerebrovascular network, with almost complete unilateral occlusion of the internal carotid artery along with compensatory collateral vessels. This led to a new diagnosis of Moyamoya disease. The patient was treated with extracranial-intracranial bypass surgery. Arterial abnormalities in patients with Moyamoya disease are uncommon and have previously only been reported in younger patients in their teens and 20s. Young and middle-aged patients presenting with central retinal artery occlusions should undergo complete neurologic workup including stroke evaluation; in this case, revealing Moyamoya disease, a rare yet life-threatening condition, as the underlying etiology.

First_Aid_Step2

Also called giant cell arteritis; due to subacute granulomatous inﬂ ammation of the large vessels, including the aorta, external carotid (especially the temporal branch), and vertebral arteries. The most feared manifestation is blindness 2° to occlusion of the central retinal artery (a branch of the internal carotid artery). Risk factors include polymyalgia rheumatica (affects almost half of TA patients), age > 50, and female gender. Presents with new headache (unilateral or bilateral); scalp pain and temporal tenderness; and jaw claudication. Fever, permanent monocular blindness, weight loss, and myalgias/arthralgias (especially of the shoulders and hips) are also seen. ESR > 50 (usually > 100). Ophthalmologic evaluation. Temporal artery biopsy: Look for thrombosis; necrosis of the media; and lymphocytes, plasma cells, and giant cells.

Isolated Infiltrative Optic Neuropathy in an Acute Lymphoblastic Leukemia Relapse.

Optic nerve infiltration as the first sign of isolated central nervous system relapse of acute lymphoblastic leukemia (ALL) is rare. A seven-year-old girl with standard-risk B-cell ALL who was in remission presented with sudden onset of left eye pain and loss of vision. Examination revealed no perception to light in the left eye with positive relative afferent pupillary defect. The optic disc was hyperemic and swollen with total obscuration of the disc margin associated with central retinal artery and vein occlusion. Magnetic resonance imaging of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement. Lumbar puncture revealed leukemic infiltration with blast cells after a week of eye symptoms, while bone marrow aspiration was negative for malignant cells. A diagnosis of left leukemic optic nerve infiltration with central retinal artery and vein occlusion was made. A high index of suspicion with repeat cerebrospinal fluid sampling is crucial to confirm the diagnosis as vitreous biopsy may fail to reveal infiltrative cells.

[The Tolosa-Hunt syndrome: report of a case with recurrent (9 times) painful ophthalmoplegia (author's transl)].

A 48-year-old woman was referred to the First Dept. of Int. Med., Nagasaki Univ. Sch. Med., in August, 1979, with a six-month history of recurrent episodes of right-sided painful ophthalmoplegia and diplopia. An epidode affected the right eye, lasted one to two weeks, and relapsed every month. On examination she had a complete ptosis on the right side and pain on the right eye. All extraocular muscle supplied by the 3rd nerve were paralysed. The pupils were equal in size both sides, reacting to light completely. Visual acuity was normal except myopia. All the other cranial nerves and the remainder of central nervous system was normal. Results of thyroid function tests and of lumbar puncture were normal. The glucose tolerance test showed a mild diabetic pattern. Blood and CSF cultures for bacteria, fungi, and acid-fast bacillus were negative. The skull, brain CT scan, and carotid angiogram were within normal limits. A tentative diagnosis of Tolosa-Hunt syndrome was made after an unproductive search for a cause for this woman's painful ophthalmoplegia and unsuccessful treatment of ophthalmoplegia with antibiotics or diet therapy for mild hyperglycemia. The patient was given prednisolone 30 mg daily orally when she had the 9th attack of painful ophthalmoplegia Pain, ptosis, and diplopia disappeared in 5 days and she did not show any recurrence of symptoms over the next 7 months.


This question is mixed hemato-nephro. It is complicated, so we are going to rule out options one by one. Option 2, nephrotic syndrome, apart from being broad and nonspecific, would not be assessable, since they do not give us the quantification of urine protein (they only tell us that urinalysis reveals the presence of kappa light chains, not the amount). Option 3 would be unlikely; in amyloidosis, the light chains that are usually deposited are of the lambda type. Option 4 also seems unlikely, since in IgA myeloma we would expect a monoclonal peak of this Ig, which in this case does not appear. The doubt that arises is between 1 and 5; I would opt for 1, because this entity fulfills the characteristics described (absence of monoclonal peak in most cases, acute renal failure and presence of kappa chains in urine), being light chain myeloma a somewhat broader entity, but option 5 could also be considered valid.

This question is mixed hemato-nephro. It is complicated, so we are going to rule out options one by one. [HIDDEN], nephrotic syndrome, apart from being broad and nonspecific, would not be assessable, since they do not give us the quantification of urine protein (they only tell us that urinalysis reveals the presence of kappa light chains, not the amount). [HIDDEN]; in amyloidosis, the light chains that are usually deposited are of the lambda type. [HIDDEN], since in IgA myeloma we would expect a monoclonal peak of this Ig, which in this case does not appear. The doubt that arises is between 1 and 5; [HIDDEN], because this entity fulfills the characteristics described (absence of monoclonal peak in most cases, acute renal failure and presence of kappa chains in urine), being light chain myeloma a somewhat broader entity, but [HIDDEN].

A 68-year-old patient consults for edema and asthenia. Laboratory tests showed creatinine 5 mg/dL, hemoglobin 10 g/dL and marked hypogammaglobulinemia in serum at the expense of IgG, IgA and IgM. A urinalysis reveals the presence of kappa light chains. What is your diagnostic suspicion?

IgA myeloma with Bence-Jones proteinuria.

[Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case].

A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years.

Plasma cell dyscrasias

Non-IgM SMM Non-IgM SMM (also termed IgG and IgA SMM because of the rarity of IgD and IgE SMM) is diagnosed in asymptomatic individuals based on criteria identical to those listed above for Non-IgM MGUS except that: their intact IgG or IgA myeloma protein levels are equal to or greater than 30 grams/liter rather than 15 grams/liter; their bone marrow shows plasma cells comprise between 10% and <60% rather than <10% of nucleated cells; and/or their 24-hour urine contains 0.5 gram or greater levels of Bence Jones, i.e. light chain myeloma, proteins. individuals must also lack evidence of more recently established multiple myeloma-defining criteria viz., CRAB features, amyloidosis, more than one solitary plasmacytoma, and/or serum or urine free light chain κ to λ or λ to κ ratios of 100 or greater.

Plasma cell dyscrasias

Individuals diagnosed with light chain MGUS typically do not express detectable levels of an IgG, IgA, IgD, IgE, or IgM intact myeloma protein in their blood. Rather, they overexpress a monoclonal, aberrant free κ (i.e. kappa) or λ (i.e., lambda) immunoglobulin light chain. For diagnosis, the κ and λ free light chains are quantified by immunological methods and the ratio of κ to λ light chains is used to detect unbalanced light chain synthesis that is indicative of a monoclonal light chain plasma cell dyscrasia. Light chain MGUS is defined as a disorder in which a serum κ to λ free light chain ratio falls outside the normal range of 0.26–1.65 (mean =0.9) provided that it is not associated with: a) any of the CRAB criteria, b) a bone marrow plasma cell count of 10 or a higher percentage of nucleated cells, c) evidence of amyloid deposition (see Light chain deposition disease), and d) an accumulation of 0.5 or more grams of the monoclonal light chain in the urine over a 24-hour period.

Plasma cell dyscrasias

Light chain SMM Light chain smoldering multiple myeloma (light chain SMM) was previously termed idiopathic Bence Jones proteinuria. The condition is currently diagnosed in asymptomatic individuals who have a 24-hour urinary Bence Jones, i.e. light chain myeloma protein level, that is >0.5 grams and/or bone marrow plasma cells that are 10% to <60% of nucleated cells. These individuals must also; lack detectable IgG, IgA, IgD, IgE, or IgM myeloma proteins in sera; have a free κ/λ or λ/κ light chain ratio outside of 0.26 to 1.65 range but less than 100; and/or have no evidence for the presence of any one of the CRAB criteria, amyloidosis, or end organ damage attributable to the myeloma proteins or plasma cells.

The clinicopathological spectrum of renal amyloidosis.

Renal amyloidosis is an uncommon cause of nephrotic syndrome. The clinical conditions in Chinese people remain obscure. This is a retrospective review of the clinicopathological spectrum of 12 cases diagnosed in Taichung Veterans General Hospital from October 1982 to November 1993. Charts and renal pathological slides were reviewed retrospectively. A scoring system was set to evaluate the degree of amyloid deposition in the renal tissue. The clinical profile, immunological data, pathological picture and final outcomes are presented and discussed, with literature review. There were 12 cases of primary amyloidosis including 1 case of multiple myeloma. All were confirmed by renal biopsy. The cases were all male with mean age of onset as 53.3 +/- 11.3 (range: 32 to 65 years). The mean follow-up duration was 22.9 +/- 32.8 months. The initial average creatinine clearance was 66.7 +/- 42.7 ml/min; mean daily urine protein was 7.0 +/- 4.1 grams. Nephrotic syndrome was the main clinical manifestation, present in all 12 cases. Other presenting symptoms and signs included: malaise in 7 cases; hypertension and anorexia in 4 cases; limb numbness in 3 cases; low back pain, dizziness and microhematuria in 2 cases each; anemia, headache, stroke, restrictive cardiomyopathy, hepatomegaly, syncope, body weight loss, dysphagia and skin itching in one case individually. Amyloid cardiomyopathy was present in 4 of the 8 patients who received echocardiography. The mean serum albumin level was 1.9 +/- 0.7 mg/dl, globulin level 3.1 +/- 1.1 mg/dl. Urinary Bence-Jones protein examination was performed in 8 cases; none revealed positive response. The mean immunoglobulin (Ig) level for the patients included: IgG 1018 +/- 901 mg/dl, IgA 262.0 +/- 313.8 mg/dl, IgM 104.8 +/- 84.2 mg/dl. There were at least 4 cases with high levels of one Ig but depressed levels in the others. M-component was shown by immunoelectrophoresis (IEP) in 90% of the cases. IEP impression in 10 cases revealed 2 cases of IgA lambda, 2 cases IgA kappa, 3 cases IgG lambda and 1 case IgG kappa monogammopathy, 1 case free lambda myeloma and 1 case negative. The ratio of kappa to lambda chain was 3:6. Bone marrow biopsy performed in 8 cases found only 1 case with multiple myeloma, one with amyloidosis; the other 6 cases were unremarkable. Mesangium was the site of heaviest amyloid deposition, followed by tubular basement membrane, artery and interstitium. The median survival time for those whose total score was lower than 3 points was 97.5 months; 3 to 5 points, 14 months; 6 points or more, 18.5 months. The median survival time was 21.6 months and 3-year-survival rate was 32.7%. The 2 cases with long-term survival were of 111 months and 84 months. The possible reason included: 1) Organ-limited renal amyloidosis; 2) Light amyloid deposition; 3) Younger age; 4) Other undetected favorable factors. 1) Renal amyloidosis is not a frequent diagnosis of nephrotic syndrome in Taiwan, but it should be suspected in every patient over 50 years old with a recent onset of proteinuria. 2) Renal amyloidosis can be diagnosed only by renal biopsy. 3) Primary renal amyloidosis is a disease of poor prognosis.

Kidney failure as an unusual initial presentation of biclonal gammopathy (IgD multiple myeloma associated with light chain disease)--a case report.

Immunoglobulin D (IgD) myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy-as-sociated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg). Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L) and renal failure dialysis rank: creatinine 1,408 micromol/L, urea 31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2 M components--massive in alpha 2 fraction of 71%; 7% in the discrete beta fraction, beta 2M / serum 110 mg / L, in urine 1.8 mg/L--extremely high; IgL kappa I lambda index 1:13 (reference value ratio 2:1). The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, lamda-light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission. The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and teamwork that can alter the course of this serious disease.

Light Chain Deposition Disease Diagnosed Using Computed Tomography-Guided Kidney Biopsy.

Light chain deposition disease (LCDD) is characterized by the deposition of monoclonal immunoglobulin light chains in the kidney, which can cause end-stage kidney disease if not treated. While kidney biopsy is required for definitive diagnosis, choosing an appropriate biopsy method may be problematic when examining patients with atrophic kidneys. A 66-year-old Japanese man was referred to our institution with a three-month history of leg edema. Clinical investigations revealed proteinuria levels of 7.5 g/day. CT-guided percutaneous kidney biopsy was selected as the biopsy method because atrophic kidneys were poorly visualized on ultrasonography. Kidney biopsy revealed nodular glomerulosclerosis, exclusive deposition of the κ chain, and powdery electron-dense deposits, all of which were indicative of LCDD. Bence-Jones protein was detected in the urine. The patient also had an abnormal serum-free light chain ratio. Bone marrow biopsy revealed multiple myeloma; therefore, the patient was diagnosed to have LCDD with multiple myeloma. The patient was treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone. After a one-year follow-up, the patient had hematological and renal responses without any treatment-related adverse effects. Our case demonstrates the effectiveness of daratumumab as a treatment for LCDD with nephrotic-range proteinuria. Additionally, we suggest that CT-guided kidney biopsy should be considered as a diagnostic test in patients with kidney atrophy when making a definitive diagnosis.

Myeloma Cast Nephropathy and COVID-19: A Case Report of Multiple Myeloma Presenting as Acute Kidney Injury in the Setting of COVID-19.

A 64-year-old African American male presented to the emergency department with subacute low back pain for two weeks and decreased urine output. He was found to have a potassium level of 9.2 mmol/L and was uremic with a creatinine level of 28.5 mg/dL and blood urea nitrogen (BUN) level of 201 mg/dL. He also tested positive for COVID-19. He was then started on continuous renal replacement therapy (CRRT). His urinalysis showed more than 500 mg/dL of protein. A workup for multiple myeloma was also conducted, and urine protein electrophoresis test was positive for free lambda light chains with a level of 17,700 mg/L and free kappa light chains with a level of 88.30 mg/L with a kappa:lambda free light chain ratio of 0.005. Additionally, serum Bence Jones protein level was elevated at 240 mg/dL, and serum beta-2 microglobulin level was elevated at 31.41 mg/L. An immunoglobulin (Ig) panel also showed low levels of IgG, IgA, and IgM. Kidney biopsy for this patient showed definite cast nephropathy and minimal chronic changes, with only one of over 20 glomeruli sclerosed and minimal interstitial deposits. The patient was started on chemotherapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD).

[IgD-lambda type multiple myeloma associated with IgG-kappa type benign monoclonal gammopathy].

A 76-year-old man was admitted to Kisen hospital because of lumbago and chest pain. Laboratory examinations revealed a chronic renal failure with marked elevation of the serum BUN (48.8 mg/dl) and creatinine levels (8.2 mg/dl). The serum electrophoresis demonstrated a hypergammaglobulinemia with M peaks. An immunoelectrophoresis demonstrated monoclonal IgD-lambda and IgG-kappa proteins in the serum, and lambda-type Bence Jones protein in the urine (0.4 g/day). Bone marrow smears revealed an abnormal proliferation of atypical plasma cells (43%). A systemic X-ray examination of the skeletal system showed systemic osteoporosis without punched out lesion. The patient was diagnosed as having IgD-lambda type multiple myeloma and IgG-kappa type benign monoclonal gammopathy by quantifying concentration of two M proteins (1,160 mg/dl in IgD, 1,179 mg/dl in IgG, respectively). A combination chemotherapy with melphalan and prednisolone was administered monthly for multiple myeloma, and hemodialysis for the renal failure was performed 3 times a week. A marked improvement of his laboratory findings including a diminution of the serum IgD-lambda M-protein was obtained. On the other hand, IgG-kappa M-protein level was unchanged. Two M-protein levels showed a different behavior after the combination chemotherapy. Although the patient died of congestive heart failure, the partial remission of multiple myeloma has been maintained for 16 months with chemotherapy.

Gamma 1-heavy chain deposition disease accompanied by IgG kappa in serum, urine, and bone marrow.

A 32-year-old Japanese woman presented with hypertension, nephrotic syndrome, microhematuria, and severe hypocomplementemia. Her serum creatinine concentration increased from 1.46 mg/dL (129.0 μmol/L) to 3.46 mg/dL (305.8 μmol/L) over 1 month. Renal biopsy revealed Congo red-negative nodular glomerulosclerosis accompanied by mesangial proliferation. There was extensive staining of immunoglobulin (Ig) G in the glomerular and tubular basement membranes and expanded mesangial regions. Staining was negative for IgA, IgM, and kappa and lambda light chains and positive for the gamma 1 IgG subclass. Staining for constant domains of the gamma heavy chains showed a deletion of the first constant domain (CH1). Electron microscopy revealed electron-dense deposits in the glomerular and tubular basement membranes and mesangium. These findings indicated gamma 1-heavy chain deposition disease (HCDD). Serum and urine immunoelectrophoresis revealed an IgG kappa monoclonal band, whereas bone marrow biopsy revealed monoclonal plasmacytosis with positive staining for kappa chains. HCDD associated with kappa light chain is extremely rare. We report the first case of HCDD with IgG kappa detected in the serum, urine, and bone marrow.

InternalMed_Harrison

The serum M component will be IgG in 53% of patients, IgA in 25%, and IgD in 1%; 20% of patients will have only light chains in serum and urine. Dipsticks for detecting proteinuria are not reliable at identifying light chains, and the heat test for detecting Bence Jones protein is falsely negative in ~50% of patients with light chain myeloma. Fewer than 1% of patients have no identifiable M component; these patients usually have light chain myeloma in which renal catabolism has made the light chains undetectable in the urine. In most of these patients, light chains can now be detected by serum free light chain assay. IgD myeloma may also present with light chain disease. About two-thirds of patients with serum M components also have urinary light chains. The light chain isotype may have an impact on survival. Patients secreting lambda light chains have a significantly shorter overall survival than those secreting kappa light chains. Whether this is due to some genetically important

[A case report of light and heavy chain deposition disease (IgG2 lambda)].

A 73-year-old male was admitted to the renal division of our hospital because of hypertension, proteinuria and bilateral pretibial edema. Eight years previously, he was diagnosed as being afflicted with interstitial pneumonia on the basis of a chest X-ray examination. Laboratory tests conducted during the current admission showed normocytic normochromic anemia, renal dysfunction and mild proteinuria. Total IgG was normal, but a high proportion of IgG2 was observed. M-protein in the serum was positive for both IgG lambda and Bence Jones protein (lambda type). A bone marrow biopsy showed the proportion of plasma cells to be 10.6%, but atypical cells were not found. We diagnosed the patient's condition as plasma cell dyscrasia. Light microscopy examination of a renal biopsy specimen showed moderate mesangial proliferation with a deposition of PAS-positive and Congo red negative materials in the mesangial area: nodular gomerulonephritis was seen in some glomeruli. Immunofluorescence revealed IgG and lambda light chains, strong linear staining along the glomerular basement membrane and tubular basement membrane and positivity in the mesangial area. Results of staining for IgA, IgM, fibrinogen and C3 were weakly positive in the mesangium area, while those for C4, Clq and free kappa were negative. Positive staining of IgG2 was seen by immunoperoxidase study, but the tissue was negative for IgG1, IgG3, IgG4. Electron microscopy demonstrated a dense granular deposition in the mesangial, subendothelial and peritubular area and a microfibrillar structure in the mesangial area. The diameter of the microfibrillar structure was 14 nm on the average.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine.

We report here a case of a 58-year-old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 microg/mL) in sera was within the normal range (0-8.0 microg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: kappa and lambda light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the lambda light chain, and negative for the amino terminus of constant region of the kappa light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow-up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.

Plasma cell dyscrasias

Multiple myeloma Multiple myeloma is diagnosed in patients that (except for non-secretory multiple myeloma patients) have a clonal IgG, IgA, IgD, or IgE myeloma protein in their serum and/or a clonal κ or λ light chain in their serum or urine plus either one of two sets of criteria. In the first criteria set, patients must have ≥10% bone marrow clonal plasma cells plus ≥1 of the CRAB criteria; in the second criteria set, patients must have ≥10 bone marrow clonal plasma cells plus ≥1 of the following findings, ≥60% bone marrow clonal plasma cells, a free κ/λ or λ/κ light chain ratio in serum of ≥100 (the involved clonal light chain concentration must be ≥100 milligrams/liter), and/or >1 focal bone lesion on magnetic resonance imaging. The 5 year medium survival of patients with multiple myeloma treated with currently used treatment regiments is 48.5%. Light chain multiple myeloma

Multiple myeloma

In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains). People without evidence of a monoclonal protein may have "nonsecretory" myeloma (not producing immunoglobulins); this represents about 3% of all people with multiple myeloma. Additional findings may include a raised calcium level (when osteoclasts are breaking down bone, releasing it into the bloodstream), raised serum creatinine level due to reduced kidney function, which is mainly due to casts of paraprotein deposition in the kidney, although the cast may also contain complete immunoglobulins, Tamm-Horsfall protein and albumin.

Fibrillary glomerulonephritis associated with monoclonal gammopathy of undetermined significance showing lambda-type Bence Jones protein.

A 79-year-old woman was admitted to our hospital because of leg edema due to a nephrotic syndrome. Urinary and serum immunoelectrophoresis showed positive for the lambda type of Bence Jones protein. A bone marrow aspiration test revealed mild plasmacytosis (6.4% of the total cells). These findings confirmed her diagnosis of monoclonal gammopathy of undetermined significance (MGUS). Her renal biopsy specimen revealed mild mesangial cell proliferation and an increase in the mesangial matrix. Immunofluorescence studies showed positive staining for IgG, IgA, C3, and kappa and lambda light chains in the capillary wall and mesangium area. Electron microscopy showed that the electron deposits in the thickened basement membrane were formed by randomly arranged 16- to 18-nm nonbranching fibrils. A Congo red stain for amyloid was negative. These findings corresponded with the diagnosis of fibrillary glomerulonephritis. Therefore, this case showed a rare combination of fibrillary glomerulonephritis and MGUS.

Plasma cell dyscrasias

Monoclonal gammopathy of undetermined significance (MGUS), is defined as the presence in the blood or urine of a monoclonal antibody, antibody heavy chain, or antibody light chain in a person lacking symptoms or signs of a more serious plasma cell dyscrasia. The condition is typically discovered as an incidental finding when serum protein electrophoresis is done for various reasons unrelated to plasma cell dyscrasias. Protein electrophoresis generally detects one of the following patterns of monoclonal myeloma protein spikes representing: a) intact IgG, IgA, IgE, IgE, or IgM; b) intact IgG, IgA, IgE, IgD, or IgM plus high concentrations of a free (i.e. not bound to a heavy chain) κ or λ light chain; c) a free κ chain in great excess of a λ chain or a free λ chain in great excess of a κ chain; and d) free γ, δ, or μ heavy chains unbound to a light chain (free α and ε heavy chain myeloma protein spikes have not been reported). Among MGUS cases expressing an intact antibody, 70%, 15%,

Plasma cell dyscrasias

Non-IgM MGUS, commonly termed MGUS, is diagnosed in individuals who exhibit a serum IgG, IgD, IgA, or IgE monoclonal protein with or without increased levels of blood and/or urine free κ or λ light chains. These patients typically also show small increases in bone marrow plasma cells. Further requirements for the diagnosis of non-IgM MGUS are: a) bone marrow clonal plasma cells <10% of total nucleated cells; b) absence of any of the four CRAB criteria (CRAB criteria are C = Calcium serum levels >1 milligram/deciliter above normal values and/or a serum level >11 milligram/deciliter; R = Renal insufficiency as defined by a glomerular filtration rate <40 milliliter/minute and/or a serum creatinine >2 gram/deciliter due to myeloma protein-induced kidney damaged; A = Anemia, as defined by a blood hemoglobin level >2 gram/deciliter below normal and/or <10 gram/deciliter due to the plasma cell dyscrasia rather than e.g. iron deficiency or blood loss; B = Bone lesions, i.e. ≥1 lytic (i.e.

Bence Jones protein

The proteins are immunoglobulin light chains (paraproteins) and are produced by neoplastic plasma cells. They can be kappa (most of the time) or lambda. The light chains can be immunoglobulin fragments or single homogeneous immunoglobulins. They are found in urine as a result of decreased kidney filtration capabilities due to kidney failure, sometimes induced by hypercalcemia from the calcium released as the bones are destroyed ,dehydration due to polyurea, amyloidosis or from the light chains themselves. The light chains have historically been detected by heating a urine specimen (which causes the protein to precipitate) and now by electrophoresis of concentrated urine. More recently, serum free light chain assays have been utilised in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma and AL amyloidosis. History

InternalMed_Harrison

PROTEINURIA ON URINE DIPSTICK Quantify by 24-h urinary excretion of protein and albumin or first morning spot albumin-to-creatinine ratio RBCs or RBC casts on urinalysis In addition to disorders listed under microalbuminuria consider Myeloma-associated kidney disease (check UPEP) Intermittent proteinuria Postural proteinuria Congestive heart failure Fever Exercise Go to Fig. 61-2 Macroalbuminuria 300-3500 mg/d or 300-3500 mg/g Microalbuminuria 30-300 mg/d or 30-300 mg/g Nephrotic range > 3500 mg/d or > 3500 mg/g + Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts)Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts) Nephrotic syndrome Diabetes Amyloidosis Minimal change disease FSGS Membranous glomerulopathy IgA nephropathy

[IgD-multiple myeloma. Review of 102 cases reported in the literature (author's transl)].

Reports on 102 patients suffering from IgD-myeloma are reviewed and analyzed. Patients with IgD-myeloma are younger than patients with myeloma producing IgG or IgA myeloma proteins.  Males are affected by this disease 3 times as often as females and 11 times as often as female patients in the group producing kappa light chain type of IgD myeloma protein. Hyperproteinaemia and extreme spikes of the monoclonal immunoglobulin occur less often. Approximately 90% of the patients have a lambda light chain myeloma protein and almost all patients excrete Bence-Jones protein. Renal insufficiency, amyloidosis, and plasma-cell leukemia are found more frequently than in other types of multiple myeloma. IgD-multiple myeloma carries a poorer prognosis, possibly related to the frequent finding of renal insufficiency.

Cryoglobulinemia

Signs and symptoms due to the cryoglobulins of type I disease reflect the hyperviscosity and deposition of cryoglobulins within the blood vessels which reduce or stop blood perfusion to tissues. These events occur particularly in cases where blood cryoglobulin levels of monoclonal IgM are high in patients with IgM MGUS, smoldering Waldenström's macroglobulinemia, or Waldenström's macroglobulinemia and in uncommon cases where the levels of monoclonal IgA, IgG, free κ light chains, or free λ light chains are extremely high in patients with non-IgM MGUS, non-IgM smoldering multiple myeloma, or multiple myeloma. The interruption of blood flow to neurological tissues can cause symptoms of confusion, headache, hearing loss, and peripheral neuropathy. Interruption of blood flow to other tissues in type I disease can cause cutaneous manifestations of purpura, blue discoloration of the arms or legs (acrocyanosis), necrosis, ulcers, and livedo reticularis; spontaneous nose bleeds, joint pain,

Plasma cell dyscrasias

IgM myeloma proteins or in rare cases other myeloma proteins such as IgA, free κ light chains, or free λ light chains may increase blood viscosity, deposit in peripheral blood vessels, and thereby cause vascular occlusion and gangrene of the extremities in the syndrome termed cryoglobulinemia. Monoclonal IgM myeloma proteins operating through their effects on increasing blood hyperviscosity can reduce blood flow to the central nervous system to cause blurred vision, headaches, vertigo, ataxia, and cold-induced hemolytic anemia. IgM, IgG, and to lesser extents κ and λ free light chain myeloma proteins can cause Immune thrombocytopenic purpura with extensive bleeding tendencies .

Plasma cell dyscrasias

AL amyloidosis can occur at any stage in the plasma cell dyscrasia spectrum. Typically, patients developing this type of amyloidosis have had excess κ or λ free light chains in their urine for years before diagnosis. At diagnosis, however, they typically have a relatively small plasma cell burden (bone marrow plasma cells <5% to 7% of total nucleated cells) and in only <5% to 10% of cases do other findings indicate the presence of a malignant condition (i.e. definitive signs of multiple myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia associated with over-production of a clonal light chain). Nonetheless, these individuals often evidence serious involvement of the kidney (proteinuria, nephrotic syndrome) or heart (restrictive cardiomyopathy, arrhythmias) in 70% or 60% of cases, respectively, and of dysfunction in the peripheral nervous system (numbness, paresthesias) or autonomic nervous system (orthostatic hypotension) in 20% or 15% of cases, respectively. They

Plasma cell dyscrasias

chain; and d) free γ, δ, or μ heavy chains unbound to a light chain (free α and ε heavy chain myeloma protein spikes have not been reported). Among MGUS cases expressing an intact antibody, 70%, 15%, 12%, and 3% express either IgG, IgM, IgA, or two of these M proteins, respectively, with or without excessive levels of a light chain; these cases represent ~80% of all MGUS. About 20% of MGUS cases express either κ or λ light chains. As a group, these MGUS findings occur more commonly in men and are ~2-fold more common in individuals of African descent than Caucasians. MGUS cases expressing free γ, δ, or μ heavy chains are extremely rare. MGUS is categorized into the following sub-types based upon the identity and levels of the myeloma proteins detected as well as the prognoses for progressive disease indicated by these myeloma protein findings.

Monoclonal Gammopathy of Undetermined Significance -- Differential Diagnosis

Monoclonal gammopathy of renal significance: This disease entity is diagnosed when the patient has diagnostic criteria for MGUS as well as renal insufficiency and monoclonal immunoglobulin deposits in the kidney by immunofluorescence. [11] Light chain smoldering multiple myeloma (idiopathic Bence Jones proteinuria): The diagnostic criteria of LC-SMM include: Monoclonal light chains in the urine (Bence Jones proteinuria) No immunoglobulin heavy chain expression in the serum or urine No symptoms of PCM, WM, or amyloid light chain amyloidosis Primary (amyloid light chain) amyloidosis and light chain deposition disease: This entity of plasma cell neoplasms is associated with the pathologic deposition of monoclonal light chains in tissue. The diagnostic criteria include the presence of amyloid in tissue and evidence of plasma cell neoplasm. B cell lymphoproliferative disorder

Multiple myeloma

Other useful laboratory tests include quantitative measurement of IgA, IgG, and IgM to look for immune paresis, and beta-2 microglobulin, which provides prognostic information. On peripheral blood smear, the rouleaux formation of red blood cells is commonly seen, though this is not specific. The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers an improvement in monitoring disease progression and response to treatment, particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain myeloma, or where the paraprotein level is very low). Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of the risk of progression from MGUS to multiple myeloma.

Distribution of heavy chain classes and light chain types in 757 cases of monoclonal gammapathies.

The distribution in heavy chain classes and light chain types of M components were studied in 757 cases of monoclonal gammapathies. These gammapathies were classified according to clinical and hematological data in 439 myeloma (MM), 165 Waldenström's macroglobulinemia (WM) and 152 monoclonal gammapathies occurring in other conditions. The IgG/IgA ratio differs in myeloma and in non-myelomatous gammapathies (64% IgG versus 33% IgA in myeloma and 95% IgG versus 5% in absence of myeloma). Presence of free light chains in patient's urines (Bence Jones proteinuria) was detected in about 72% of cases of MM, 48% of WM and only in 9% in others gammapathies. Concerning the sex of patients, an equal repartition between males and females is observed in MM, whereas males predominate in WM. The age distribution of the patients shows that 74% of myeloma and 79% of WM were above sixty. In addition to the 757 cases under study, 10 sera with two M Components were characterized.

Diagnosis of light chain cast nephropathy through immunostaining of the urine: Perfecting the "liquid biopsy".

Light chain (LC) cast nephropathy is the main cause of kidney injury and an important determinant of poor survival in patients with multiple myeloma (MM). It is usually suspected when an MM patient with elevated serum concentration of free LC presents kidney failure, but it often requires confirmation by kidney biopsy. We report the case of a 73-year-old woman who presented with fatigue, weight loss, and constipation. Laboratory exams revealed anemia, hypercalcemia, and kidney failure. Urine sediment analysis demonstrated irregular crystalline "waxy type" casts. With the hypothesis of LC cast nephropathy, immunostaining of the urine sediment was performed. The analysis revealed several rectangular and irregular casts with intense and bright stain for λ LCs only. A myelogram was performed, showing extensive occupation of the bone marrow by plasma cells; and immunofixation in urine and serum revealed monoclonal IgG-λ component, confirming the diagnosis of IgG-λ MM. This case highlights the potential utility of the urine sediment analysis and immuno-staining as a reliable non-invasive alternative method for diagnosis of cast nephropathy in patients with monoclonal gammopathies.

Plasma cell dyscrasias

Increases in the levels of free κ or λ light chains are a common feature of plasma cell dyscrasias. These increases occur in: 40% of IgM MGUS, IgM SMM, and Waldenstroms macroglbulonemia cases; 60% to 70% of non-secretory multiple myelom cases; 90% to 95% of intact immunoglobulin multiple myeloma cases; and, by definition, 100% of light chain multiple myeloma cases. There are two different types of plasma cell dyscrasia-associated amyloidosis syndromes: amyloid light chain amyloidosis (AL amyloidosis) in which amyloid deposits consist of free light chains and amyloid heavy chain amyloidosis (AH amyloidosis) in which amyloid deposits contain only free heavy chains. The deposits in a third type, AHL amyloidosis, consists of both free light chains and free heavy chains. AHL amyloidosis is here, as in some recent reports, grouped with AH amyloidosis.

Serum free light-chain measurement

Guidelines In 2009, the International Myeloma Working Group published guidelines making recommendations of when serum free light-chain analysis should be used in the management of multiple myeloma. Diagnosis The serum free light-chain assay in combination with serum protein electrophoresis and serum immunofixation electrophoresis is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL amyloidosis which requires all the serum tests as well as 24 h urine immunofixation electrophoresis. Monitoring Serial serum free light-chain measurement should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease. It should also be done in all patients who have achieved a complete response to treatment to determine whether they have attained a stringent complete response.

Efficacy and safety of plasmapheresis in symptomatic hyperviscosity and cast nephropathy: A Multicenter Experience in Turkey.

Cast nephropathy (CN) and hyperviscosity (HV), which we encounter in plasma cell diseases, are serious clinical manifestations that increase mortality and morbidity if not managed well in the early period. Therapeutic plasma exchange (TPE) procedures based on the removal of patient plasma is a frequently preferred treatment modality. TPE is recommended at varying levels of evidence for the treatment of CN and HV in plasma cell disorders. A total of 61 patients, 50 with multipl myeloma (MM) and 10 with Waldenström macroglobulinemia (WM), who underwent TPE for CN and HV, were included in our multicenter, and retrospective study. A statistically significant decrease was found in all disease-related biochemical markers, which were measured 1 week after the application of TPE added to standard medical treatment (IgG; p < 0.001, IgM; p = 0.004, IgA; p = 0.14, kappa light chain; p < 0.001, lambda light chain; p < 0.001, β-2 microglobulin; p < 0.001, total protein; p < 0.001, albumin; p < 0.001, LDH; p = 0.02, creatine; p < 0.001, hemoglobin; p = 0.010). Clinically, all 11 patients who underwent TPE for HV responded. While a partial response (PR: 80 %) was obtained in 40 of 50 MM patients with CN, no response was obtained in 10 patients (non-response: 20 %). In conclusion, it was observed that TPE reduced all biochemical markers related to HV and CN, while making a significant contribution to clinical improvement. We believe that adding TPE to the standard treatment in this patient group will reduce mortality and morbidity in the early period and have a positive effect on survival in the long term.