A 28-year-old African American woman presented to the emergency department with a four-month history of increased thirst, fatigue, intermittent headaches, myalgias, nausea, and a 20-lb unintentional weight loss. She has never been diagnosed with medical conditions requiring chronic medication use. She reported uveitis of the right eye in the summer of 2021, which was treated with topical steroids and subsequently improved. She was never prescribed a thiazide diuretic. She does not take antacids or herbal supplements. She does not have a significant smoking history. She works as an assembly line worker for a car company. She had similar symptoms two weeks prior to this admission and was found to have a high calcium level (16.3 mg/dL; reference range: 8.5-10.5 mg/dL) and a high ionized calcium level (7.36 mg/dL; reference range: 4.48-5.28 mg/dL). She was admitted, and investigations revealed a normal TSH (1.08 uIU/mL; reference range: 0.40-4.50 microIU/mL), low vitamin D, 25OH (9 ng/mL; reference range: 30-100 ng/mL), low vitamin A (20.1 mcg/dL; reference range: 32.5-78.0 mcg/dL), a serum protein electrophoresis with decreased total albumin and protein, and a high 24-hour urine calcium test (416 mg/24 hr; reference range: 100-300 mg/24 hr). AST was high (41 U/L; reference range: <35 U/L), while ALP and ALT were within normal limits. She was found to have an acute kidney injury secondary to pre-renal disease that improved with IV fluids. Calcium levels decreased, and she was discharged home with a plan to follow up outpatient for further workup of hypercalcemia. However, the same symptoms recurred before appointments could be arranged, along with additional symptoms of intermittent blurring of vision, dry eyes, and dry mouth.
On admission, she was found to have tachycardia and low blood pressure. A physical exam revealed no palpable cervical, supraclavicular, or axillary lymphadenopathy. The lungs were clear to auscultation bilaterally. There was a note of dense breast tissue on the upper outer quadrant of her left breast. An abdominal exam revealed a non-tender and non-distended abdomen with normoactive bowel sounds. She had no disturbance to consciousness and had the intact sensation of light touch and normal motor strength on all her extremities. Her tendon reflexes were normal, and there was no noted pathologic reflex.
Her laboratory testing revealed high levels of calcium (13.7 mg/dL; reference range: 8.5-10.5 mg/dL) but normal Parathyroid hormone (PTH; 8 pg/mL; reference range: 8-72 pg/mL) and PTH-related peptide (PTHrp) levels (0.9 pmol/L; reference range: <=4.2 pmol/L). Given the initial laboratory results, there was a suspicion of sarcoidosis, and so an angiotensin-converting enzyme (ACE) level and an IL-2 (interleukin-2 receptor) level were checked, both of which were found to be high. The ACE level was >120 U/L (reference range: 7-60 U/L) and the IL-2 level was 3654.5 pg/mL (reference range: 175.3-858.2 pg/mL). Further work-up revealed an elevated creatinine (1.43 mg/dL; reference range: 0.50-1.10 mg/dL), high vitamin D-1,25 OH (172 pg/mL; 19.9-79.3 pg/mL), negative Sjogren's antibodies A and B, normal lipase (4 U/L; reference range: 7-60 U/L), normal C-telopeptide (534 pg/mL; reference range: 25-573 pg/mL for premenopausal) and a complete blood count with peripheral blood smear revealing microcytic hypochromic anemia, mild lymphopenia, and mild monocytosis with adequate reticulocytosis. Serum-free light chains showed a high free kappa (3.58 mg/dL; reference range: 0.33-1.94 mg/dL), normal free lambda (2.59 mg/dL; reference range: 0.57 to 2.63 mg/dL), and a normal free kappa/lambda ratio (1.38; reference range: 0.26-1.65). Ultrasound of the abdomen showed a 7mm non-obstructing calculus in the mid-right kidney. Chest X-ray revealed no hilar lymphadenopathy or acute process (Figure 1).
Considering the patient's history, physical exam findings, and diagnostic work up until then, further investigations to rule out malignant lymphoma and breast cancer were carried out.
Serum tumor markers CA 15-3 (28.8 U/mL; reference range: 0.0-31.9 U/mL), CA 27.29 (38.4 U/mL; reference range: <38.6 U/mL), and CEA (0.7 ng/mL; reference range: 0.0-3.0 ng/mL) were all within normal range. A CT of the chest, abdomen, and pelvis with contrast revealed mild nonspecific splenomegaly with nonspecific upper mediastinal, left hilar, and left supraclavicular adenopathy up to 10 mm and mildly enlarged upper abdominal and retroperitoneal lymph nodes up to 10-17 mm (Figures 2-4).
A bone scan showed no suspicious radiotracer uptake within the axial or appendicular skeleton. PET scan showed moderate uptake involving the bilateral parotid and submandibular glands, redemonstration of the patient's splenomegaly, as well as left supraclavicular, thoracic, and upper abdominal lymphadenopathy with mild FDG uptake. Because of the absence of palpable lymph nodes on physical exam and no probable targets for excisional biopsy seen on imaging, a bone marrow biopsy was performed and showed a normocellular bone marrow with trilineage hematopoiesis and small noncaseating granulomas (Figure 5). No evidence of malignancy was noted.
An infectious workup showed a past EBV infection (EBV VCA IgG >750 U/mL (reference range: 0.0-17.9 U/mL), EBV nuclear antigen IgG 443.0 U/mL (reference range: 0.0-17.9 U/mL); otherwise, the workup was negative for TB, syphilis, coccidioides, histoplasma, and blastomyces. At this point, the patient reported that she had noticed skin changes in the tattoo on her right upper arm in the last few months. She reported that it became more pruritic and mildly painful, with associated skin thickening and scaling. A biopsy of the tattoo revealed multiple well-formed, non-caseating granulomas containing tattoo pigment in the dermis. It was negative for fungal elements or bacterial colonies (Figure 6). Based on the patient's history, physical examination, and laboratory findings, a diagnosis of extrapulmonary sarcoidosis with cutaneous, splenic, lymph node, and bone marrow involvement was made.
Our patient was started on oral prednisone 40 mg daily, after which she was started on a long-term tapering regimen that was completed after seven months. Shortly after starting treatment, she clinically improved. Of note, a month after starting steroid therapy, she was started on hydroxychloroquine 200 mg daily as a steroid-sparing agent as she started experiencing increased appetite and weight. As of the time of this writing, the patient has had no recurrence of her symptoms. A repeat CT of her chest six months after starting treatment also demonstrated an interval decrease in lymphadenopathy and splenomegaly.