Due to poor general condition, severe stomatitis and involvement of lips paraneoplastic pemphigus was excluded by indirect immunofluorescence on rat and monkey bladder, immunoblotting with extract from cultured keratinocytes (containing full length periplakin, envoplakin, and desmoplakin I/II), and envoplakin ELISA (Euroimmun) [2].

The patient was in a reduced general condition with signs of systemic illness including tachycardia and hypotension, for what he received noradrenalin infusions. After 2 days on the Intensive Care Unit (ICU), we initiated a combination treatment with immunoadsorption on three consecutive days (1 cycle) and an i.v. dexamethasone pulse (100 mg/day for three consecutive days) followed by high-dose i.v. immunoglobulins (IVIG; 2 g/kg of body weight) and an increase of the mycophenolate mofetil dose to 2 g/day (Fig. 5.2). Daily wound care consisted of antiseptic (polihexanide or alginate hydrogel) and non-adhesive wound dressings. Due to the pain associated with oral food intake, parenteral nutrition was necessary to provide adequate nutritional support. In fact, dehydration, hypovolaemia and electrolyte abnormalities necessitated intravenous fluid replacement of up to 7 l per day. The patient was embedded in an air-fluidized temperature-controlled bed on laminated sheets and synthetic dressings. After no improvement of pemphigus lesions for 2 weeks, a single cyclophosphamide bolus (600 mg i.v.) was administered, rituximab treatment was initiated (four infusions of 375 mg/m² in weekly intervals) and the second cycle of immunoadsorption and IVIG was given.

Unfortunately, the patient’s overall clinical condition rapidly deteriorated with high fever and increased CRP serum levels necessitating transfer to the ICU for cardio-respiratory support. The patient developed septic shock, with Staphyloccocus aureus, Acinetobacter baumanii, Enterococcus and Candida species identified in blood cultures. Tailored antibacterial and antifungal therapy including, daptomycin, caspofungin, meropenem, ceftazidim, linezolid, voriconazol, vancomycin, tigecyclin and anidulafungin was employed over 5 weeks. The patient was intubated and ventilated for 8 days. Acute renal failure required dialysis for 3 days. While the systemic infection markedly improved mucocutaneous lesions persisted. Consequently, topical clobetasol 0.05 % ointment (up to 300 g/day) and oral prednisolone (2 mg/kg) were initiated and after 1 week increased to 2.25 mg/kg. Two additional cycles of immunoadsorption and IVIG were given at 3 week intervals (Fig. 5.2). After 5 weeks the patient was discharged from ICU to the dermatology ward and mucocutaneous lesions started to improve allowing the cessation of treatment with topical corticosteroids steroids and tapering of the oral prednisolone dose. IVIG was further administered on a monthly basis while mycophenolate mofetil had to be reduced and later omitted due to increasing pancytopenia that was finally attributed to cytomegalovirus reactivation. Systemic antiviral therapy with valganciclovir for 8 weeks led to disappearance of the virus load. Ongoing bacteremia and systemic Candida infections required repeated systemic antimicrobial and antifungal therapy. Severe hyperkalaemia due to adrenal gland suppression was managed on ICU for few days. Since mucocutaneous lesions only healed slowly rituximab 1 g was given. However, the patient could be mobilized following intensive physiotherapy and was discharged to a rehabilitation hospital after nearly 6 months in our clinic with hydrocortisone 30 mg/day. He still had erosions on the back, upper arms, shoulders, nates and thighs covering about 1–2 % of his body surface corresponding to a PDAI of 18 (Fig. 5.3). Anti-desmoglein autoantibody levels had decreased by 97 % compared to admission (Fig. 5.2).

IVIG cycles were continued together with i.v. dexamethasone pulses (100 mg/day for three consecutive days) 4- and subsequently, 5-weekly. At present, 11 months after the first presentation in our department, the patient has a small post-traumatic erosion on his right upper arm while mucosal lesions had disappeared (Fig. 5.4). Anti-desmoglein 3 autoantibody levels are 71 U/ml with no anti-desmoglein 1 serum reactivity detectable (Fig. 5.2).