Extensive Palpable Purpura Preceding Renal Dysfunction in Immunoglobulin A Vasculitis Due to Coronavirus-19 Infection

Presentation

A gentleman in his 80s with a history of heart failure, stage II chronic kidney disease, and hypertension presented with a 3-week history of dyspnea and non-productive cough, in addition to a 1-day history of palpable purpura of the lower extremities and buttocks. The patient denied any recent travel, sick contacts, or new medications. The patient had previously received 3 COVID-19 vaccinations, with the third vaccine administered 6 months prior to presentation.

On presentation, vitals were as follows: temperature 36.9°Celsius, blood pressure 132/60 mmHg, heart rate 92, and oxygen saturation 94% on room air. Physical examination demonstrated palpable purpura of his bilateral lower extremities and buttocks. Over the following 24 hours, the palpable purpura coalesced and extended to include his abdomen, back, bilateral forearms, palms, dorsal hands, and lateral face (Figure 1 ).

Figure 1.

Extensive palpable purpura in a patient with IgA vasculitis due to COVID-19 infection. (A) Palpable purpura of the bilateral lower extremities. (B) Palpable purpura of the buttocks and low back. (C) Palpable purpura and swelling of the bilateral dorsal hands and forearms. (D) Palpable purpura of the bilateral palms. (E) Palpable purpura of the abdomen. (F) Involvement of the lateral face.

Assessment

Laboratory analysis was significant for hemoglobin 9 g/dL (baseline 10 g/dL), white blood count 10.9 × 10⁹/L, platelets 304 × 10⁹/L, and serum creatinine (sCr) 1.1 mg/dL (baseline). Pro-brain natriuretic peptide n-terminal was normal. Liver transaminases were normal. Point of care COVID-19 rapid nasal swab was negative. Urinalysis was significant for trace protein and 7 red blood cells. Chest radiograph showed mild pulmonary edema with small bilateral pleural effusions. Computed tomography chest angiogram showed scattered mixed consolidative and ground-glass opacities in the lungs.

A skin biopsy demonstrated leukocytoclastic vasculitis with direct immunofluorescence showing granular, perivascular deposits of immunoglobulin M, immunoglobulin A, C3, and fibrin around the upper dermal blood vessels (Figure 2 ). Due to the absence of systemic findings at this time, treatment was not started.

Figure 2.

Skin pathology in a patient with immunoglobulin A vasculitis due to COVID-19 infection. (A and B) Hematoxylin and eosin sections showed superficial and mid-dermal perivascular inflammatory infiltrates composed of predominantly neutrophils with scattered lymphocytes and eosinophils. There is marked red blood cell extravasation and focal fibrinoid necrosis (arrow) of the blood vessels. (C) The direct immunofluorescence showed granular, perivascular deposits of immunoglobulin A around superficial dermal blood vessels.

Although the patient's sCr had been at baseline on admission, it rose to 1.9 mg/dL by day 8. Urine studies were notable for a protein to creatinine ratio 1163 mg/g. Nephrology recommended initiation of methylprednisolone 60 mg daily on hospital day 8 and renal biopsy on hospital day 12 due to continued rise in sCr despite steroids. Renal biopsy showed IgA nephropathy with mesangial proliferation, endocapillary hypercellularity, and rare glomerular crescents (Figure 3 ).

Figure 3.

Renal pathology in a patient with immunoglobulin A vasculitis due to COVID-19 infection. (A and B) On hematoxylin and eosin stain, the majority of glomeruli showed endocapillary hypercellularity with abundant neutrophils and focal segmental tuft necrosis. (C) Immunofluorescence showed strong, predominantly mesangial, granular glomerular staining for immunoglobulin A.

Diagnosis

Bronchoscopy completed hospital day 18 showed normal bronchial mucosa and anatomy. Infectious studies from bronchoalveolar lavage were significant for positive COVID-19 real-time polymerase chain reaction. An infectious, autoimmune, and oncologic evaluation was otherwise negative.

Management

The patient was treated with high-dose steroids and supportive care for IgA vasculitis. He received methylprednisolone 60 mg daily before transitioning to an oral steroid taper. Rituximab for treatment of IgA vasculitis was considered but not given due to COVID-19 infection.

The patient's sCr peaked at 2.3 mg/dL on hospital day 24 with continued proteinuria and hematuria. At discharge on hospital day 45, the patient's serum creatinine was stable at 2.0 mg/dL. He was discharged to a rehabilitation facility on prednisone 40 mg daily.

At the 1-month post-hospital follow-up, the patient's sCr was 3.0 mg/dL. The degree of proteinuria had worsened with albumin to creatinine ratio of 1845.07 mg/g. At the 3-month post-hospital evaluation, the patient's sCr was stable at 3.1 mg/dL. Proteinuria had improved with albumin to creatinine ratio of 415.15 mg/g. Given improvement in albuminuria, the patient's prednisone 40 mg daily was slowly tapered. Although proteinuria had improved at the 3-month post-hospital follow-up, the patient's renal function had not returned to pre-hospital baseline. His rash had resolved besides erythematous, pruritic non-blanching plaques involving his right lateral arm.

Discussion

Immunoglobulin A vasculitis is a leukocytoclastic vasculitis of small vessels with predominant IgA immune complex deposition.¹ Though IgA vasculitis is more common in children, disease occurs in adults with an annual incidence of 0.1 to 1.8 per 100,000 individuals.¹ Clinical manifestations of IgA vasculitis include enteritis, arthritis, renal impairment, and palpable non-thrombocytopenic purpura of the lower extremities and buttocks.² Infectious precipitants of IgA vasculitis are most commonly group A Streptococcus, parainfluenza virus, human parvovirus B19, and Heliobacter pylori.³

The most common skin manifestations seen with COVID-19 infection are morbilliform rash, urticaria, vesicular eruptions, vaso-occlusive manifestations (including livedo racemosa and retiform purpura), and pernio-like acral lesions.⁴ Pernio-like acral lesions, described as an idiopathic cold-sensitive inflammatory disorder manifesting with violaceous macules, papules, plaques, or nodules at sites of cold exposure, typically denote mild systemic disease, whereas retiform purpura is seen more commonly in critically ill patients.⁴ Immunoglobulin A vasculitis due to COVID-19 infection with palpable purpura of the lower extremities has been described in case reports.^{2 , 5 , 6}

Although the pathophysiology of COVID-19-induced IgA vasculitis has not been fully elucidated, it is thought that COVID-19 infection may hyper-stimulate the immune system, leading to excessive neutrophil-associated cytokine responses, immune complex deposition in tissues, and molecular mimicry.⁶ At the time of writing of this report, 15 cases of IgA vasculitis due to COVID-19 infection have been described in the literature.^{2 , 5 , 6} Each of these patients received steroids, and 4 patients received immunosuppressive therapy with rituximab, mycophenolate mofetil, or cyclophosamide.² In addition to the reports of IgA vasculitis described above, there have also been reports of IgA nephropathy after COVID-19 infection.^{7 , 8} Debate is ongoing as to whether IgA vasculitis and IgA nephropathy represent clinical manifestations on a continuous spectrum of 1 disease, with IgA vasculitis as the systemic form of IgA nephropathy.⁹

Treatment of IgA vasculitis is controversial and includes supportive and pharmacologic management.¹ For IgA vasculitis-associated nephritis, consensus guidelines recommend corticosteroids as a first-line treatment, with consideration of azathioprine, mycophenolate mofetil, or cyclophosamide, although evidence to support these immunosuppressants is lacking.¹⁰ Per these guidelines, for an extensive, rapidly progressing rash, a short course of steroids, azathioprine, or both, can be considered. Plasmapheresis, intravenous immunoglobulin, and rituximab can also be used as alternative therapies in refractory or relapsing IgA vasculitis.¹⁰

In this case, the patient's point of care (POC) nasal swab on presentation was negative for COVID-19. It is likely that the POC test on presentation was a false negative, given symptoms and imaging on presentation consistent with COVID-19 infection. Although we cannot prove causality of COVID-19 infection leading to IgA vasculitis, a comprehensive infectious work-up was pursued and was otherwise negative. Given absence of other etiology, he was diagnosed with IgA vasculitis due to COVID-19 infection.

In this case, extensive palpable purpura preceded renal dysfunction. In patients with COVID-19 infection who have extensive palpable purpura, IgA vasculitis should be considered in the differential diagnosis. It is not known whether extensive palpable purpura is a predictor of more severe IgA vasculitis. Physicians should be aware of the potential for COVID-19 infection to lead to IgA vasculitis with palpable purpura. Furthermore, clinicians should be aware of the potential for skin manifestations to precede organ dysfunction. Further research is needed to elucidate whether early recognition and treatment of IgA vasculitis with skin manifestations prevents further organ involvement and damage.

Uma Paniker, MD, Section Editor