New Onset Granulomatosis with Polyangiitis Associated with COVID-19

The coronavirus disease 2019 (COVID-19) has recently been found to cause cutaneous vasculitis in patients. Granulomatosis with polyangiitis (GPA) is a type of small and medium vessel vasculitis that is often associated with pulmonary issues and has been shown to raise diagnostic complications in COVID-19 infection. In this report, we discuss the first case of new-onset GPA in the setting of active COVID-19 infection. Symptoms often overlap between the two diseases, and while there is no current cure for COVID-19, rapid immunosuppressive initiation can be lifesaving for patients with GPA. Thus, this case is essential in expanding our current knowledge of COVID-19 and its many skin manifestations.


Introduction
e coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, while clinicians have been compelled to continuously expand their knowledge base of this novel complex disease and its associated symptoms. Several coronavirus patients have been found to have vascular endothelial damage, which is thought to play a role in the development of both skin lesions [1] and strokes [2]. Several dermatologists report seeing a vasculitis-like eruption in COVID patients [3,4]. Herein, we discuss a case of new onset granulomatosis with polyangiitis (GPA), a small and medium vessel vasculitis, associated with a suspected case of COVID-19.

Case Presentation
In April 2020, a 46-year-old man with a past medical history of diabetes presented to the emergency room with symptoms of cough, shortness of breath, and fevers for four weeks. He was treated for suspected pneumonia with azithromycin two weeks prior to presentation and denied any improvement in respiratory symptoms thereafter. In addition, he developed a painful and pruritic rash that was progressively worsening over the last two weeks (see Figure 1 for timeline of patient course).
On physical examination, he was afebrile (36.9 C) with tachycardia (110 bpm), blood pressure 127/77 mm Hg, respiratory rate 20, and O 2 saturation 94% on room air. He had erosions on bilateral nasal mucosa and vermillion lips with overlying crusts. Oropharynx was clear. ere were purpuric macules and papules on bilateral palms, arms, and legs, few with overlying vesicular changes and collarettes of scale (Figures 2(a) and 2(b)). He also had retiform purpuric macules and patches on buttocks and thighs (Figure 2(c)), as well as ulcerations on buttocks at the gluteal cleft.
Based upon his clinical presentation, histologic findings, and laboratory studies, the patient was diagnosed with GPA in the setting of suspected coronavirus infection. He was first treated for coronavirus with five-day course of hydroxychloroquine, followed by treatment of GPA with systemic steroids and rituximab infusion. Kidney function improved, and his rash completely resolved. He was discharged on a steroid taper.

Discussion
We discuss a case of c-ANCA-positive granulomatosis with polyangiitis possibly triggered by a COVID-19 infection. Our patient presented with four weeks of symptoms and had negative nasopharyngeal PCR test; however, positivity to RT-PCR begins to decline three weeks after initial symptom onset [5]. Furthermore, a review of 8,136 pooled specimens showed RT-PCR positivity using nasopharyngeal swabs to be a mere 45.5% (compared to bronchoalveolar lavage with 91.8%) [6]. Our patient showed positive IgM antibodies to COVID-19, owing to possible recent infection, although there has been a report of cross-reactivity to COVID-19 IgM serological testing in GPA [7]. We are hesitant to conclude this case as a false-positive, rather we hypothesize patient's delayed presentation and low-yield specimen for PCR testing may have missed an active or recent COVID-19 infection (as illustrated in Figure 1).
Infections or viruses can trigger GPA [8], and without treatment, it has a devastatingly high mortality rate [9]. First-line therapies are either rituximab or cyclophosphamide. Glucocorticoids can also be given, especially for maintenance therapy. In the setting of coronavirus, there is a concern that immunosuppressive therapies could increase the likelihood of adverse events including hospitalization and mortality [10,11]. However, other studies suggest that the increased risk of COVID-19-related adverse events (such as admission to an intensive care unit or requiring mechanical ventilation) is minimal, and outcomes are improved when patients are on immune-modifying medications [10,12]. Furthermore, patients given   Case Reports in Dermatological Medicine dexamethasone, a well-known immunomodulatory therapy, had significantly lower mortality and length of hospital stay [11]. Disclosure e corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Conflicts of Interest
e authors declare that there are no conflicts of interest.

Authors' Contributions
Moshe Bressler and Naeha Pathak contributed to literature search and writing. Kelly Cervellione, Farshad Bagheri, MD, and Edward Epstein, MD, contributed to case write up. Adnan Mir, MD, and Rebecca Tamez, MD, were responsible for data collection and case write up obtained pathology photos.