Scleroderma Renal Crisis and COVID—Is There an Association?

Scleroderma renal crisis (SRC) is a rare but potentially devastating complication of systemic sclerosis as it is associated with significant morbidity and mortality. We present an interesting case of a patient who developed SRC following infection with COVID-19. A 37-year-old female presented with new-onset hypertension, AKI, anemia and thrombocytopenia. She had a history of diffuse cutaneous systemic sclerosis diagnosed 8 years ago, that had been well controlled with immunosuppression. The patient had contracted COVID-19 infection about 2 weeks ago but had remained largely asymptomatic except for a sore throat. Urinalysis revealed sub-nephrotic proteinuria but was otherwise bland. Peripheral blood smear was notable for 12-15 schistocytes per HPF. ADAMTS13 and complement levels were normal. Serologies for ANA, ANCA, anti-Scl70, anti-Jo1, anti-Sm, lupus anticoagulant, anti-beta2-glycoprotein I, anti-RNA polymerase III, RF, cryoglobulin, RPR, hepatitis and HIV, all returned negative. Renal biopsy revealed an arterial predominant thrombotic microangiopathy (TMA) (Figure) consistent with a diagnosis of SRC. The patient was treated with anti-hypertensives including an ACE-inhibitor, but her AKI continued to worsen, ultimately leading to dialysis dependence. SRC classically develops in patients with early or progressive diffuse cutaneous disease or positivity for anti-RNA polymerase III antibodies. Our patient did not have any such risk factors and rather developed SRC following infection with COVID-19. COVID-19 has been reported to cause TMA by inducing immune dysregulation via an overactive complement system. It is plausible that infection with COVID-19 triggered an exaggerated immune response, in turn leading to the development of SRC in our patient. COVID-19 may trigger SRC in patients with systemic sclerosis in the absence of other risk factors. (Figure Presented)

GETTING TO THE HEART OF THE MATTER

CASE: 45-year-old woman with PMHx systemic sclerosis presents with fever, weight loss, chest tightness, weakness and altered mental status for 2 weeks. Home meds are prednisone, mycophenolic acid, lasix. On presentation she is febrile to 38.9C, HR 110, BP 97/64, SpO2 96% on RA. Exam shows telangiectasis, normal cardiopulmonary exam, mild sclerodactyly. Oriented only to self, has bilateral LE 3/5 weakness. Labs with WBC 2.6K, Hgb 7.1, plts 126K. Cr normal. Liver enzymes mildly elevated. BNP 3900. Trop 251. Lactate 4.9 Blood cultures negative, CMV/EBV negative, COVID-19 negative, Ferritin > 15,000, Triglycerides 274 LDH 495, Fibrinogen 274, D-Dimer 755, ANA 1:1280, + dsDNA, low titer Smith, + RNP, + SSA, + RNA Pol III. TTE with EF 27% and diffuse hypokinesis. Cardiac MRI with myocardial fibrosis no active myocarditis, suggestive of scleroderma. Lumbar puncture with high protein, borderline increased oligoclonal bands, elevated IgG index but elevated synthesis rate, suggestive of CNS inflammation. Patient is in cardiogenic shock secondary to hemophagocytic lymphohistiocytosis/macrophage activating syndrome (HLH/MAS) related to systemic sclerosis/scleroderma with SLE overlap requiring inotropes and aggressive diuresis. She develops severe pain and bright red purpura on bilateral legs. Hypercoagulable w/u showed low protein C/S, low complement, negative cryoglobulin. Skin biopsy showed vaso-occlusive process c/w HLH/MAS. Receives IV methylprednisolone for empiric treatment of HLH/MAS and IV cyclophosphamide for possible lupus cerebritis. Patient improves and is discharged on long-term milrinone, Plaquenil, and steroids. IMPACT/DISCUSSION: Secondary HLH or MAS is a life-threatening condition of extreme inflammation that can occur in autoimmune conditions, infection, or malignancy Diagnosing HLH requires high clinical suspicion - >10K ferritin level is highly sensitive and specific for diagnosis of HLH This patient has multisystem involvement of autoimmune disease given history of scleroderma The LP studies raise concern for lupus cerebritis, specifically the IgG index and IgG synthesis rate are helpful for this diagnosis Underline subtype of systemic sclerosis-overlap syndromes and here particularly scleroderma lupus overlap Highlight the utility of cardiac MRI in characterizing myocarditis / fibrosis Discuss need for high alert for necrotizing fasciitis with painful palpable purpura Overview treatment of HLH/MAS with high dose steroids Reflection on high mortality of HLH/MAS and question of recovered heart function CONCLUSION: Teaching Point 1: Secondary HLH is a syndrome of extreme inflammation caused by underlying malignancy, autoimmune condition, or infection. Teaching Point 2: HLH and MAS have a great deal of symptom/clinical presentation overlap. Ferritin level > 10,000 is highly sensitive and specific for diagnosis of HLH Teaching Point 3: Systemic sclerosis can present in a variety of ways including cardiac, lung, skin involvement.