**1. Introduction**

Currently, we are facing a global pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While vaccines diminished the number of new infections, hospital admissions, and deaths, the number of so-called breakthrough hospital admissions of fully vaccinated individuals is increasing. Vulnerable patients with immunosuppressive medication, in particular, are at high risk of suffering from severe symptoms during an infection. In addition, there is always a part of the population that is not vaccinated. This can be due to underlying medical conditions or because a few individuals refuse to be vaccinated. Studies reported that immunosuppressed and multimorbid patients have a poor immune response following the SARS-CoV-2 vaccination [1]. In addition, experiences with other coronaviruses showed that immunosuppression could lead to atypical presentations including prolonged incubation periods, a persistence in asymptomatic viral shedding, and atypical symptoms such as gastroenterological disease and encephalitis. Experience and research evidence on COVID-19 in such patients are still very limited [2–7]. The severity of the COVID-19 infection is correlated with age, as well as gender and comorbidities such as cardiovascular diseases, diabetes, chronic respiratory diseases, hypertension, and cancers. A measured high number of white blood cells and neutrophils, as well as elevated D-dimer levels, are observed in COVID-19 patients with severe outcomes [8,9].

Pyoderma gangrenosum (PG) is a rare and chronic neutrophil inflammation. It belongs to the spectrum of autoinflammatory diseases and is characterized by recurrent episodes of

**Citation:** May, M.R.; Rübben, A.; Lennertz, A.; Vanstreels, L.; Leijs, M. Dealing with Corticosteroid and High-Dose Cyclosporine Therapy in a Pyoderma Gangrenosum Patient Contracting a COVID-19 Infection. *J. Pers. Med.* **2022**, *12*, 173. https:// doi.org/10.3390/jpm12020173

Academic Editors: Mircea Tampa, Monica Neagu, Constantin Caruntu, Simona Roxana Georgescu and Carolina Constantin

Received: 28 November 2021 Accepted: 24 January 2022 Published: 27 January 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

progressive and often painful sterile inflammation. PG can be found solitary and multiple. According to Frank C. Powell (1996), six forms can be classified [10]. The classic and most frequent form is the ulcerous form. It develops fast and is mostly laminar. PG is a rare disease, as the global incidence is estimated to be around three to ten cases per one million population per year [9]. Moreover, it is frequently associated with several comorbidities especially inflammatory intestinal diseases (IBDs) (25%) [11], autoimmune disease (14.1%), hematological disorder (6.2%), and others (17.2%) [9]. PG is more often present in women than in men and most prevalent in 50–70-year-old individuals. Diagnosing PG properly is indispensable since PG is linked with a major reduction in quality of life and even with death [8]. To avoid misdiagnosis the Delphi score (D), as well as the so-called PARACELSUS score (P), which is an acronym, considers the following criteria (Table 1) [12,13]:


**Table 1.** The Major and Minor Criteria of the Delphi and PARACELSUS score.

\* The Paracelsus score contains three additional criteria: suppurative inflammation in histopathology, undermined wound border, systemic disease associated.

The pathogenesis of this autoinflammatory disease is not just multifactorial but also still unknown. In addition, the different PG types are differing in pathogenesis according to their form. Abnormalities in the function of the immune system including inflammatory cytokines, neutrophilic dysfunction, and specific genetic mutations have been observed. Evaluation of 21 patients with PG demonstrated infiltrates of CD-31 T cells and CD-1631 macrophages with high levels of interleukin (IL)-8 in the lesion. As IL-8 is a potent chemotactic for neutrophils, this explains the typical neutrophilic infiltrates, which can be visible in histopathological examination [14]. Overexpression of interleukin (IL)-1β plays an important role in PG as well but is not specific [15]. It has been suggested that PG and rheumatic diseases share a commonality in T-cell abnormalities. It was proposed that autoreactive T cells, which destroy pilosebaceous units, contribute to the pathophysiology since complete hair loss is found after healing [16]. An elevation of several chemotactic cytokines and interleukins was found in another study: CXC motif chemokine ligand

(CXCL) 9, CXCL 10, CXCL 11, chemokine C-C ligand 3 (CCL-3) and CCL-5, interleukin (IL)- 36G, IL-17A, IL-8 (a neutrophil chemokine), and interferon gamma have been identified in PG lesions. In addition, an upregulation of certain transcription factors (STAT 1 and STAT 4) responsible for promoting Th1 differentiation was found in another study [17]. Very rare PG can appear as a monogenetic disease such as the PAPA syndrome in which case it is accompanied by arthritis and cystic acne [18]. Early diagnosis of pyoderma gangrenosum is important in order to minimize the size and necrotic painful character of the ulcer, as well as the formation of disfiguring scars [16]. In addition, secondary bacterial infections can occur and should be prevented.

Immunocompromised patients, including those requiring immunosuppressive therapy following autoinflammatory skin disease, are at high risk for developing severe disease following SARS-CoV-2 infection [2]. Neither the data regarding the best medical management of immune-compromised patients testing positive for SARS-CoV-2 nor strategies for reducing or modifying immunosuppression are easy to standardize yet [2]. In this case, in this study, we describe a 58-year-old man who became infected with COVID-19 while being treated with (high-dose) corticosteroids and cyclosporine. As cases similar to this are not commonly discussed, the aim of this paper was to set an example for other clinicians of how an adjustment of immunosuppressive therapy in patients with a rare autoinflammatory disease such as PG contracting a COVID-19 infection could be successfully performed.
