koreich in 1981 first reported the case of a 22 year old man diagnosed as hodgkin lymphoma ( hl ) who developed hypothermia and hypotension during the course of his admission , which resolved only after initiation of chemotherapy .
systemic symptoms are present in a third of patients at presentation and among them fever is the most common followed by night sweats and weight loss . on review of literature , we found 18 case reports with similar finding of hypotension and hypothermia associated with hl .
most of the patients in these case reports developed hypotension and hypothermia after initiation of chemotherapy .
only 3 out of these 18 patients were found to have hypotension at the time of presentation prior to diagnosis .
we report the case of a patient who presented with hypotension and hypothermia and was diagnosed initially with septic shock .
he was found to have ill - defined liver lesions on the computed tomography ( ct ) scan which were new on comparison with a recent ct abdomen done for evaluation of nephrolithiasis .
the pathophysiology of development of hypotension and hypothermia in patients during chemotherapy or prior to diagnosis remains unexplained .
a complex interaction between cytokines , tumor and blood vessels has been proposed as the genesis of such a presentation .
a 61 year old man presented to emergency room with history of flank pain on right side , dysuria , urgency and frequency with occasional hematuria for 3 days associated with fever , chills and rigors .
3 weeks before this presentation he was admitted for renal colic and was found to have a new staghorn calculus in the kidney which was managed conservatively with 7 days of oral antibiotics .
review of systems noted a history of 40 pounds weight loss over 3 months , drenching night sweats and occasional low grade fevers for last 3 months .
past medical history was significant for multiple episodes of renal colic secondary to nephrolithiasis treated with lithotripsy several years ago .
social history was significant for 30 pack year history of smoking , occasional alcohol consumption and no substance abuse or high risk behavior .
was noted to be hypotensive with a blood pressure ( bp ) of 78/49 mmhg and mean arterial pressure ( map ) of 59 mmhg .
the hypotension was new compared with recent admission 3 weeks prior , where the bp readings were consistently above a map of 80 .
the hypotension did not correct with bolus of 3 liters of 0.9% normal saline ( ns ) and in view of his history of dysuria and intermittent hematuria and recent diagnosis of staghorn calculus he was diagnosed with urinary tract infection ( uti ) leading to urosepsis and septic shock .
he was admitted to medical intensive care unit ( micu ) where he was started on pressor support with norepinephrine and broad spectrum antibiotic coverage with vancomycin and piperacillin - tazobactam .
vitals recorded at presentation were temperature of 97.3f , bp of 78/49 mmhg , map of 59 mmhg , heart rate 80/min , respiratory rate 18/min , spo2 of 98 - 99% on room air .
general exam was significant for an averaged sized man in mild distress with mild pallor , no icterus , cyanosis or edema .
labs were significant for hemoglobin ( hb ) of 9.2 g / dl , mean corpuscular volume ( mcv ) of 77.6 fl and leukocyte count ( wbc ) of 5.1 k/l with differential of 77% neutrophils .
liver enzymes showed alkaline phosphatase of 212 u / l , alanine transaminase ( alt ) 80 u / l , aspartate tranaminase ( ast ) 96 u / l , total protein 3.6 g / dl and albumin 1.5 g / dl .
urine dipstick was positive for blood ( 1 + ) , proteins ( 30 ) and glucose ( 50 ) and urine microscopy showed 109 rbc and 12 wbc .
two sets of blood culture and urine culture were done prior to starting antibiotics which showed no growth after 5 days of incubation .
ct scan abdomen done at presentation showed numerous ill defined lesions in the liver which were new from the ct scan done 3 weeks before for evaluation of renal colic ( figure 1 ) .
the study redemonstrated the staghorn calculus with no evidence of obstruction , no radiographic evidence of pyelonephritis or renal abscess .
patient received 2 days of pressor support with norepinephrine drip , following which his blood pressure improved to a map over 70 mmhg , however he continued to have intermittent episodes of hypotension which were managed with frequent boluses of 1000 to 500 ml of 0.9% ns .
interestingly , on day 5 of admission , patient developed increased shortness of breath and became hypoxic .
trans - thoracic echocardiogram done at bedside showed normal ejection fraction and normal inferior vena cava .
patient was diagnosed with fluid overload secondary to frequent fluid boluses and was given one dose of 20 mg i.v .
lasix which led to resolution of shortness of breath . during this entire stay , he continued to have intermittent episodes of hypotension with mean arterial pressure dropping to low 60 s .
colonoscopy and esophago - gastro - duo - denoscopy ( egd ) done as part of malignancy workup , showed 2 polyps which were diagnosed as tubular adenoma and thick gastric folds with chronic gastritis on histopathology respectively .
a liver biopsy was planned after improvement in his overall condition however on day 9 of the hospitalization patient declined the procedure and requested a break from the hospital .
liver biopsy was deferred for a later date and patient was discharged in a stable condition . during this
admission 4 blood cultures and 3 urine cultures did not show any growth after 5 days of incubation .
he was discharged with oral levofloxacin to complete a course of 14 days of antibiotics for complicated uti .
three days after being discharged from hospital , patient returned to emergency room with similar complaints of acute onset weakness and fatigue and a single episode of fever for which he received a single dose of ibuprofen at home .
vitals at presentation showed rectal temperature of 94.1f , bp of 84/49 mmhg , mean arterial pressure of 60 mmhg , breathing at rate of 18/min , heart rate 59/min and saturating 97% on room air .
patient was readmitted to micu with a provisional diagnosis of urosepsis and was given vancomycin and piperacillin - tazobactam . blood culture and urine culture
done at this time again showed no growth which could support the diagnosis of sepsis .
biopsy of the liver lesions showed extensive lymphocytic and histiocytic infiltrates with abnormally large cells and positive stains for cd15 and cd30 .
bone marrow biopsy also showed areas of residual trilineage hematopoesis with 40% cellularity alongwith several para - trabecular infiltrates composed of large atypical cells including reed - sternberg ( rs ) cells , in a mixed inflammatory background consisting of small lymphocytes , histiocytes , eosinophils and plasma cells ( figure 2 ) .
the immuno - histochemical stains were positive for cd15 and cd30 and negative for cd45 , cd3 and cd20 .
a 100 cell count showed granulocytes ( 56% ) , monocytes ( 1% ) , eosinophils ( 6% ) , erythroid precursors ( 34% ) , lymphocytes ( 2% ) and plasma cells ( 1% ) .
the presence of the characteristic rs cell in a mixed inflammatory background pointed towards a diagnosis of hl .
the diagnosis was further confirmed by positive immune - histo - chemical ( ihc ) stain for cd15 and cd30 along - with negative ihc stain for cd45 , cd3 and cd20 .
since no pan - t antigens were missing , the possibility of a t - cell lymphoma was very low . a ct chest for staging did not show any hilar lymphadenopathy .
soon after the diagnosis patient was started on chemotherapy with doxorubicin , dacarbazine , vinblastine .
bleomycin was initially withheld due to unknown pulmonary function in view of patient been active smoker and was added later after pulmonary function test turned out to be normal .
after completion of the 1 cycle of chemotherapy the blood pressure started improving to a map of more than 80 mmhg ( figure 3 ) . at 6 month
follow up the patient continues to be free of any episode of hypotension or hypothermia .
reported the first patient with hl who developed hypothermia and hypotension during the course of admission , prior to initiation of chemotherapy . since then 18 more cases have been reported with hypothermia as presenting feature and in 8 out of 18 patients , hypotension has also been recorded ( table 2 ) .
fifteen out of 18 patients reported in literature had developed these symptoms after initiation of chemotherapy with only 3 patients presenting with hypotension prior to diagnosis .
interestingly , most of the patients described with hypothermia and hypotension have been reported to have liver metastases . to date
, the mechanism behind hypotension and hypothermia as isolated manifestations of hl remains unexplained . in our patient
though the presentation of the patient was highly suggestive of urosepsis , numerous blood and urine cultures did not grow any microbe which could have explained the cause of sepsis .
moreover treatment with vancomycin and piperacillintazobactam did not lead to improvement in the condition of the patient , essentially ruling out infectious cause and sepsis as the primary cause of hypotension .
an increased random and morning cortisol level and tsh / free t4 level ruled out adrenal insufficiency and thyroid involvement respectively .
a normal transthoracic echocardiogram demonstrated a normal cardiac anatomy and clinically there were no signs of heart failure .
though orthostatic maneuver was not done in our patient because of his general condition , the absence of correction of hypotension with volume repletion and fluid boluses makes hypovolemia less likely .
blood pressure control is governed by a complex interaction between cardiac , renal , endocrine and nervous systems .
hypotension in cancer patients has long being believed to be secondary to cytokine release from increased macrophage function .
the cytokines implicated in causing hypotension are interleukin ( il)-1 and il-2 , tumor necrosis factor- ( tnf- ) and interferon- ( if- ) .
although the exact mechanism of tnf- causing hypotension is not clear , it is well known that administration of tnf- leads to production of nitric oxide ( no ) which is a potent vasodilator and could lead to hypotension .
in addition to this , cytokines also cause endothelial damage , a mechanism which is very well defined in patients with sepsis and septic shock . in patients with sepsis infection
another important association implicated in this patient is the effect of psycho - neuroendocrine hormones in mediation of no , like melatonin , which has been shown to have counter - regulatory effect on action of free radicals , especially no .
we postulate from the above , that the probable cause of hypotension in this patient could be release of cytokines from the tumor especially from liver metastasis , which is an extremely vascular organ .
autonomic dysfunction is a know paraneoplastic syndrome associated with hl which raises the possibility of direct infiltration of hypothalamus or pineal gland by the tumor leading to alteration in neuroendocrine hormones .
the loss of inhibition of counter - regulatory effects of these hormones on cytokine regulation could result in macrophage activation and no production resulting in hypotension .
our patient never took any salicylates for his fever which rules this out as a possible cause .
moreover , not all patients reported were taking nsaids before presentation , making this explanation less likely . in conclusion
although , further studies are needed in support of this association , we can conclude from this case that the condition responds dramatically to aggressive chemotherapy .
 hypotension is an extremely rare manifestation of hodgkin lymphoma . 
 we report the case of a patient who presented with new onset hypotension and was diagnosed with urosepsis and septic shock requiring pressor support for maintaining his blood pressure . 
 computed tomography ( ct ) scan of abdomen showed liver lesions , which were new on comparison with a ct abdomen done 3 weeks back . 
 biopsy of the liver lesions and subsequently a bone marrow biopsy showed large atypical reed - sternberg cells , positive for cd15 and cd 30 and negative for cd45 , cd3 and cd20 on immuno - histochemical staining , hence establishing the diagnosis of hodgkin lymphoma . 
 the mechanism involved in hodgkin lymphoma causing hypotension remains anecdotal , but since it is mostly seen in patients with advanced hodgkin lymphoma , it is hypothetically related to a complex interaction between cytokines and mediators of vasodilatation . here 
 we review relevant literature pertaining to presentation and pathogenesis of this elusive and rare association . 
Introduction
Case Report
Discussion and Conclusions