Haemophagocytic Lymphohistiocytosis with Stevens-Johnson Syndrome Masquerading as Sepsis

Dear Editor, Haemophagocytic lymphohistiocytosis (HLH) or haemophagocytic syndrome is a severe hyperinflammatory syndrome characterized by fever, cytopenia, splenomegaly, decreased natural killer (NK) cell function and biochemical features of excessive inflammation. We report a case of secondary form of HLH in a 45-year-old female with Stevens-Johnson syndrome (SJS) due to its rarity. A 45-year-old female presented with dusky red macules, vesicles over the face, trunk, and extremities and epidermal detachment over the trunk covering nearly 8% of the body surface area with mucosal erosions and haemorrhagic crusting after intake of unknown medications for joint pain [Figure 1]. On day 1, the SCORTEN score was 2, and the patient was started on injectable steroids, broad-spectrum antibiotics and oral cyclosporine (100 mg twice daily) along with appropriate topical management. Biopsy from the lesion over the trunk was confirmatory of SJS [Figure 2]. The patient’s condition improved for the first two days with the drying of erosions, stable vitals and investigations. After day 3, her condition deteriorated with persistent pyrexia (104° F), pancytopenia, transaminitis, coagulopathy, electrolyte imbalance and hypoalbuminemia over 5–6 days. All inflammatory markers were elevated. Wound swabs, blood cultures, fever profiles and procalcitonin levels were sent to rule out sepsis, and all were negative. Soluble CD25 levels (2800 U/ml) and triglyceride levels (380 mg/dl) were raised [Table 1]. Our case satisfied five out of eight of the 2004 criteria for HLH.[1] Hence, the final diagnosis of SJS complicated by HLH was reached. On day 10, she was shifted to the medicine intensive care unit and started on noradrenaline drip and 4 l of oxygen, but she succumbed to her condition on the same day before bone marrow aspiration. Molecular diagnosis of HLH could not be performed due to financial constraints.Figure 1: (a–e) Dusky red macules to patches over face, chest, abdomen back and thighs with oral and ocular erosions with epidermal detachment at placesFigure 2: (a, b) Full-thickness epidermal necrosis, sparse dermal inflammatory infiltrate. (a: 10×; b: 40×, H and E stain)Table 1: Clinical and laboratory parameters of the patientHLH can be primary (familial) or secondary (non-familial). Secondary HLH is generally triggered by infections, immunosuppressant drugs, and malignant or rheumatological disorders and has seldom been reported with SJS.[1] In HLH, there is uncontrolled macrophage cell activation and failure of normal negative feedback from cytotoxic T-cells or NK cells.[2] Both toxic epidermal necrolysis (TEN) and HLH are characterized by defective activation of cytotoxic CD8+ lymphocytes and elevation of serum granulysin, which is likely an explanation of the association of the two entities.[3] There are very few reports of the association of SJS/TEN and HLH worldwide [Table 2]. Since the presentation of SJS with sepsis and SJS with HLH is very similar, it can be challenging for clinicians to suspect HLH in the setting of SJS. CD25 is a useful inflammatory marker correlating with disease activity. Hyperferritinemia has 90% sensitivity and 96% specificity, while hemophagocytosis has 83% sensitivity and 60% specificity in the diagnosis. Pancytopenia (at least two cell lineages) is a common feature of HLH, and SJS has less chance of developing pancytopenia; hence, it can be considered an early indicator for SJS complicated by HLH and enables prompt diagnosis.[4] Early diagnosis and aggressive management are essential for improving patient prognosis. Various treatment modalities, including intravenous immunoglobulin, Cyclosporin A, high-dose steroids, intrathecal methotrexate, etoposide, plasma exchange, bone marrow transplantation and, most recently, Ruxolitinib, have been described.[1]Table 2: Association of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and haemophagocytic syndromeThis case is reported to create awareness among clinicians to differentiate HLH from underlying conditions or infection in SJS patients with prolonged fever, refractory cytopenias and hepatitis. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.