**2. Case Report**

We present a 58-year-old Caucasian European male with an extremely painful ulcer at his right lateral malleolus (see Figure 1a). Anamnesis revealed that the wound appeared after massage therapy that he received for Achilles tendinitis. Initially, he reported a painful bulla, which became ulcerative. Due to other physical problems (otitis media and necrosis of the temporomandibular joint) and the fact that he was taking antibiotics and analgesics, the patient did not seek medical treatment at an earlier stage of the disease. However, the wound expanded within two weeks rapidly and became very painful. Medical history revealed comorbidities of diverticulosis and hypercholesterolemia.

**Figure 1.** Pictures of the ulcer: (**a**) at the time of hospitalization; (**b**) healed ulcer 8.5 weeks after initial diagnosis.

Clinical evaluation revealed a 4 cm × 8 cm ulcer with tissue necrosis, as well as a very painful livid erythematous encircling undermined edge (Figure 1a). No signs of venous insufficiency were visible. Clinical assessment showed normal peripheral vascularization.

An infectious ulcer was excluded by a negative microbiological swab. Peripheral arterial occlusive disease and venous insufficiency could be excluded with duplex sonography. Computed tomography of the foot and ankle was used to exclude osteomyelitis.

Two skin biopsies were taken from the edge of the ulcus. As seen more often in PG, histopathological findings were not specific. However, the dermis showed fibrosis including mixed cellular inflammatory infiltrates. These were mainly perivascular lymphocytic but also mixed lymphohistiocytic infiltrates including some neutrophil granulocytes. Infiltrates contained mostly CD-3 positive T lymphocytes.

We diagnosed the ulcer as an ulcerating form of pyoderma gangrenosum due to its typical clinical presentation and as the minor criteria (Delphi) and major and minor criteria of the PARACELSUS score of pyoderma gangrenosum (which is discussed in detail in the Introduction Section) were fulfilled [12].

We decided to start directly a combination therapy with (2.5 mg/kg) cyclosporine A (CsA) twice a day and systemic methylprednisolone (1 mg/kg) per day because of severe pain and a rapidly increasing wound (despite premedication with 20 mg methylprednisolone from the patients' otorhinolaryngologist) and in order to avoid side effects of long-term steroid usage [8]. A local corticosteroid and a calcineurin inhibitor ointment were applied once a day, and an adsorbing dressing was added.

An improvement in pain and a decrease in ulcer size were observed. Moreover, the C-reactive protein (CRP) declined satisfactorily under this treatment. After 5 days of treatment, the CRP declined from 198.3 mg/L (see Table 2) to 37.7 mg/L (RV < 8.0).


**Table 2.** The laboratory parameters at the time of the patient's hospitalization.

Five weeks after the initial hospitalization, the patient presented to the emergency care with fever and dyspnea. At this time, he was still taking 300 mg CsA and 8 mg methylprednisolone. A PCR test (long nasal swab) confirmed the SARS-CoV-2 infection. Computer tomography demonstrated typical lung infiltration (Figure 2). It had to be decided whether to continue or modify the immunosuppressive therapy or to interrupt cyclosporine A since cyclosporine interferes with the antiviral immune pathway [3]. We decided to halve the cyclosporine A dosage to 75 mg twice a day (Figure 3). The patient's clinical condition significantly improved within three days from the beginning of COVID-19 symptoms. The ulcer healed 8.5 weeks after the initial diagnosis (Figure 1b).

**Figure 2.** Typical COVID-19 lung infiltrates, five weeks after initial presentation.

**Figure 3.** Timeline of patient's healing and the dose of methylprednisolone and cyclosporine A.
