An uncommon diagnosis of a young female with fever of unknown origin (FUO): Idiopathic Hemophagocytic Lymphohistiocytosis (HLH)

Abstract

Background. Hemophagocytic Lymphohistiocytosis (HLH), characterized by uncontrolled activation of immune cells leading to a hyperinflammatory state, is seldom considered in the initial differential diagnosis of FUO. The rarity of idiopathic HLH, especially in young individuals without an identifiable trigger, emerges as an uncommon and particularly challenging diagnosis. This case report presents a compelling narrative of a young female grappling with the complexities of FUO, ultimately revealing the rare and life-threatening entity of idiopathic HLH. Case report. A 25 year old female was referred to our hospital in view of persistent high grade fever since 3 months. Patient has no other complaints. Vitals stable. General and systemic examination normal. Lab investigations showed a total leukocyte count 18000 cell/μL, hemoglobin 9.2 g/dL, and platelets 68000 cells/μL. Other blood investigations showed erythrocyte sedimentation rate (ESR) 88 mm/h, C-reactive protein 21 mg/L, ferritin 670 ng/mL, triglyceride 281 mg/dL, and fibrinogen 1.2g/L. She also had transaminitis with AST 80, ALT 92 and ALP 1442. The entire infectious diseases panel was done which came negative for all, including viral serologies and hepatitis markers. Procalcotonin level was normal and no other relevant investigations came positive. Autoimmune panel analysis also came negative. Blood cultures came negative in two different samples. Also, there is no evidence of vegetation in echocardiography. Coming to the invasive investigations, bone marrow biopsy and aspiration were done to arrive at a diagnosis and it showed Hemophagocytosis. Endoscopy and colonoscopy were done, which came normal. CT thorax and abdomen also showed no significant abnormality, ruling out the probability of missing any gross malignancies. After all this extensive work up and according to Hscore, which is used to estimate an individual’s risk of having reactive hemophagocytic syndrome, this patient was diagnosed with HLH. According to the current HLH guidelines, initial treatment for the disease consists of etoposide, corticosteroids (dexamethasone), or cyclosporine is given for 8 weeks. The patient was started on the same above treatment regimen, but only with corticosteroids for a period of 8weeks, after consultation with Hematologist. No recurrence is seen in her 6-months of follow-up. The regimen was well tolerated by the patient. Studies also have shown that therapeutic plasma exchange also has a role in HLH treatment, which can be tried in familial and relapsing cases. Conclusion. In our case, this young female was diagnosed to have Idiopathic HLH, after ruling out all the familial and secondary causes of HLH including Infections, Malignancy and Autoimmune diseases. The patient was also started on treatment early after the bone marrow and other relevant investigations according to HScore suggested the diagnosis of HLH and the patient improved accordingly. Hence, apart from clearly knowing the etiology or clinical manifestations, HLH is associated with a high mortality rate if appropriate treatment not given. Generally, the underlying etiology determines the prognosis of the disease. But, it is not a good idea to delay the treatment in order to find the cause and type of HLH, because the exhaustive work up might lead to unacceptable delays in improvement and prognosis of the patient. The diagnostic work up and treatment should be done simultaneously in the patient, which has been done in our case and it lead to a good outcome. Though HLH is a fatal and dangerous disease and also highly challenging to make a diagnosis due its uncommon and largely variable clinical presentation, smart work up and early initiation of treatment will lead to better prognostic outcome.

Keywords

• hlh
• fever of unknown origin
• young female
• idiopathic