Purpura Fulminans and Transient Nephrotic Range Proteinuria: Rare Manifestation of Leptospirosis

To the Editors: An 11-year-old male child presented to the emergency department in a state of septic shock. He complained of high-grade fever, purpura fulminans, altered sensorium and seizures for the last 5 days (Fig. 1). He was immediately stabilized, intubated for poor Glass Gow Coma scale (E2V1M5) and other supportive care was started. Empirical antimicrobials included ceftriaxone and vancomycin. He had leukocytosis (20 × 103/L; neutrophils 80%, lymphocytes 18%), thrombocytopenia (60 × 103/L) and elevated C-reactive protein (21.9 mg/dL). Malaria, scrub typhus and blood cultures were negative. Punch biopsy from skin lesions and cerebrospinal fluid latex agglutination studies ruled out meningococcemia. The patient developed nonoliguric acute kidney injury (AKI, stage 3; estimated glomerular filtration rate, 46 mL/min/1.73m2; blood urea, 11.15 mmol/L and serum creatinine, 0.11 mmol/L). Urine examination revealed proteinuria (3+), but no hematuria. Spot urine protein creatinine ratio was highly raised (6.35). He also developed transaminitis (serum glutamic-oxaloacetic transaminase, 6.71 µkat/L, serum glutamic pyruvic transaminase, 7.91µkat/L), without jaundice. Serum IgM antibodies by enzyme-linked immunosorbent assay for leptospirosis were positive (National Centre for Disease Control). He was then started on intravenous doxycycline. AKI was managed conservatively. He improved subsequently, was extubated successfully on day 7 of intensive care unit admission, and was shifted to the ward.Figure 1.: Left panel shows purpura fulminans during active infection. Right panel shows purpura fulminans during recoveryLeptospirosis is an infectious and emerging public health zoonotic disease caused by the spirochetes bacteria Leptospira spp. The clinical course of leptospirosis is variable. Most cases are mild and self-limited or subclinical, while some are severe and potentially fatal, such as aseptic meningitis and hepatorenal dysfunction.1 Rash in leptospirosis may be transient truncal maculopapular erythematous, lasting for a day. But frank purpura fulminans is not described (Fig. 1).2 At admission, Purpura fulminans rash was violaceous in color, irregular margins and was present mainly over lower limbs. Over the next 10 days, the rash became darker and blackish, coalesced and grew. Its progress halted only after 2 weeks. Purpura is frequently caused by meningococcus, streptococcus and staphylococcus infections.3 Pathophysiology includes consumption of protein C, S and antithrombin III, creating a prothrombotic state. Thrombosis of dermal vessels ensues, along with hemorrhagic necrosis.3 In this case, purpura involved all 4 limbs and started fading after 3 weeks. AKI (in about 60% of cases) is known in leptospirosis along with mild proteinuria. Urinalysis may show pyuria, granular casts and occasionally microscopic hematuria. The case fatality rate of AKI due to leptospirosis is approximately 22%. Heavy proteinuria in the nephrotic range is rare. Our patient had a very high urine protein/urine creatinine ratio of 6.35. This persisted even when the child became afebrile. Improvement in proteinuria started after 2 weeks of illness. We could find only 1 case report of nephrotic range proteinuria (9 g/day).4 We kept meningococcemia as the first possibility in view of acute meningoencephalitis, septic shock, thrombocytopenia and purpura fulminans but workup for the same was negative. Leptospira contains endotoxins in its outer membrane in the form of lipopolysaccharides, lipoproteins and peptidoglycans. These antigenic irritants can potentially cause vasculitis and renal tubular, glomerular inflammation, and dysfunction.5