key: cord-0990698-rlijntwk authors: Jedlowski, Patrick M.; Jedlowski, Mahdieh F. title: Coronavirus disease 2019‐associated immunoglobulin A vasculitis/Henoch–Schönlein purpura: A case report and review date: 2021-11-05 journal: J Dermatol DOI: 10.1111/1346-8138.16211 sha: e8c1975716657895cdacd5b7416d1415a4aba3df doc_id: 990698 cord_uid: rlijntwk Immunoglobulin A (IgA) vasculitis or Henoch–Schönlein purpura is a predominantly pediatric disease occurring after a triggering viral or bacterial infection. Conversely, drug exposure is the most common inciting event in adult cases of IgA vasculitis. Recently, data has suggested a temporal association between coronavirus disease 2019 (COVID‐19) and the development of IgA vasculitis in children and adults. Here, we describe a case of IgA vasculitis with nephritis in a 70‐year‐old man with COVID‐19 and perform a comprehensive review of eight reported cases of suspected COVID‐19‐associated IgA vasculitis. When compared to classical IgA vasculitis, COVID‐19‐associated IgA vasculitis exclusively affects males (p < 0.00002) and is more common in adults (p < 0.005). Among cases of COVID‐19‐associated IgA vasculitis, adult cases were associated with significantly more arthralgia than pediatric cases (p = 0.04). In cases where skin biopsy was obtained, direct immunofluorescence (DIF) was negative for IgA in 50% of cases; thereafter, kidney biopsy DIF was positive for IgA in all cases. With this study, we provide support for an association between IgA vasculitis and severe acute respiratory syndrome coronavirus 2 infection and provide clinical information differentiating its manifestations from classical IgA vasculitis. diarrhea and bilateral symmetrical arthralgias of the wrists, ankles, and knees, and presented with abdominal pain, diarrhea, and a purpuric rash on the bilateral lower extremities, buttocks, and abdomen. An intranasal swab for SARS-CoV-2 antigen was positive on admission; he had not received COVID-19 vaccination. Physical examination revealed palpable petechiae on the bilateral dorsal feet and pedal arches with extension proximally onto the bilateral thighs and abdomen, where purpuric plaques were noted ( Figure 1 ). Laboratory investigations were notable for elevated erythrocyte sedimentation rate and C-reactive protein to 40 mm/h (reference range, 0-20) and 7.71 mg/dL (reference range, 0-8), respectively. The patient's urine protein/creatinine ratio was 4479 mg/g (reference range, 0-30 mg/g creatinine) and urinalysis was notable for 28 red blood cells (RBC)/high-power field (HPF) (reference range, 0-3). He was prescribed 6 mg oral dexamethasone for 8 days and thereafter lost to follow-up for 1 month and returned with hematochezia and acute kidney injury, evidenced by worsening of serum creatinine from baseline of 0.8 mg/dL (reference range, 0.7-1.4) to 3.8 mg/dL. Urinalysis revealed gross hematuria with 315 RBC/HPF and urine protein/creatinine ratio of 1790 mg/g creatinine. Punch biopsy of a purpuric plaque on the abdomen with hematoxylin-eosin (HE) was notable for leukocytoclastic vasculitis (LCV). Direct immunofluorescence (DIF) was notable for strong signal granular IgA deposition and weaker signal C3, C5B-9, and fibrinogen deposition surrounding the vasculature of the superficial papillary dermis. A kidney biopsy HE demonstrated mesangial hypercellularity, focal/mild endocapillary hypercellularity, tubular atrophy, interstitial fibrosis, and lymphocytic tubulitis, without crescents. DIF showed granular mesangial deposition of IgA (2+), with identification of patchy effacement of podocytes on electron microscopy. He was diagnosed with IgA vasculitis, and he was prescribed methylprednisolone 500 mg i.v. for 3 days followed by prednisone 1 mg/kg p.o. At 1-month follow-up, the patient had significant improvement of creatinine to 2.1 mg/dL, improvement in urine protein/creatinine ratio to 505.6 mg/g, and resolution of abdominal pain and rash. The patient provided written informed consent to publication of his case details. A literature review was performed which identified nine cases of IgA vasculitis associated with a diagnosis of COVID-19, in addition to our case (Table 1) . [3] [4] [5] [6] [7] [8] [9] [10] [11] Three of these cases 4,6,11 lacked biopsy data and another 10 reported LCV on skin biopsy but lacked positive confirmatory IgA screening with immunostaining or DIF. However, these cases met European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society criteria for HSP and were included. 12 All reported cases of COVID-19-associated IgA vasculitis were in males, as opposed to the slight male sex predilection (56-57%) seen in other IgA vasculitis cases reported previously (χ 2 -test, p = 0.005). 2 Pediatric patients represented five of 10 (50%) cases with patients aged 4 years or less comprising three of these. The remainder oc- Organs involved included the skin, joints, gastrointestinal tract, and renal systems. Acute kidney injury and proteinuria occurred exclusively in adult patients. However, when adult and pediatric cases were compared for differences in clinical presentation, arthralgias reached statistical significance (p = 0.04) while proteinuria approached statistical significance (p = 0.07) ( Table 2 ). There was no difference in organ system involvement between adult and pediatric patients. Nine of 10 cases were treated with corticosteroids. In the 10th case the patient was treated with acetaminophen. Follow-up information was available in seven cases; six cases received corticosteroids with improvement. The case treated with acetaminophen had persistence of rash and microscopic hematuria. The pathogenesis of COVID-19-associated IgA vasculitis may be related to faulty development of a type 2 T-helper (Th2) response to the virus and development of IgA vasculitis. 13 Patients with more severe cases of COVID-19 inappropriately mount a Th2 response, resulting in the activation of B cells and production of antibodies. 13 Presumably, given the high antigen load, a type 3 hypersensitivity reaction occurs with accumulation of antigen-antibody complexes. 13 Resultant deposition of antigen-antibody complexes, most commonly in blood vessels, occurs with subsequent activation of the complement cascade and release of complement anaphylatoxins (C3a and C5a), 13 None. None declared. Patrick M. 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