BACKGROUND:It has been previously shown in a relatively small group of patients that a combination of immunoadsorption (IA) and rituximab with daily use of high-dose oral corticosteroids and azathioprine/mycophenolate mofetil may induce a rapid and durable remission in severe, treatment-resistant pemphigus.OBJECTIVES:To achieve a more rapid reduction of serum autoantibody levels by a more frequent use of IA in the initial phase of treatment and to reduce the number of severe adverse events of continuous oral corticosteroid therapy by switching to pulsed intravenous applications.METHODS:Twenty-three consecutive patients with severe pemphigus were included. IA was performed at initially 3- and later 4-week intervals until lesions healed by 90%; 1000mg rituximab was given at weeks 1 and 3, and intravenous dexamethasone pulses were administered at first every 3weeks and then at increasing intervals in addition to daily azathioprine/mycophenolate mofetil.RESULTS:Along with a fast and durable decline of circulating autoantibody levels, all patients showed improvement of pemphigus lesions within the first weeks of therapy and long-term complete remission was induced in 19 (83%) patients. In the remaining four patients, one (4%) minimal disease and three (13%) partial remissions were observed. Over the long-term follow-up of 11-43 (mean 29) months, six (26%) patients had a recurrence and in two (9%) patients, severe adverse events occurred.CONCLUSIONS:This novel protocol treatment induces a fast and long-term remission in severe pemphigus and seems to offer an improved side-effect profile compared with daily use of corticosteroids.

Mucous membrane pemphigoid (MMP) is clinically characterized by predominant involvement of mucous membranes which in case of conjunctival lesions can lead to blindness. In MMP, autoantibodies are directed against different proteins of the dermal-epidermal junction; in 25% of cases, laminin 332 is the target. Anti-laminin 332 MMP with ocular involvement is particularly difficult to treat. A 46-year-old Caucasian man with anti-laminin 332 pemphigoid and extensive oral and nasal erosions as well as severe conjunctival involvement did not respond to intravenous dexamethasone-cyclophosphamide pulses combined with oral cyclophosphamide. After initiation of a therapeutic regimen originally established for the treatment of pemphigus, including immunoapheresis and rituximab in combination with intravenous dexamethasone-cyclophosphamide pulses and oral mycophenolate mofetil, lesions cleared within 4 months and circulating autoantibody levels became undetectable 3 months later. This is the first report of the successful use of adjuvant immunoapheresis and rituximab in previously treatment-refractory anti-laminin 332 MMP.

Anamnese: Seit 2005 Exzision mehrerer Talgdrüsentumoren. Aktuell rasche Größenprogression neuer Hautveränderungen an Wangen, Nase, Stirn und Decolleté. Vorbekannte CLL mit Z.n. div. Chemotherapien. Prozedere: Radikalexzision des Nodus an der Nase (sekundärer Wundverschluss mittels Spalthauttransplantat) sowie Exzision multipler Nodi parasternal rechts, an der Stirn sowie an der Schläfe rechts (jeweils primärer Wundverschluss). Histologische Identifizierung von Talgdrüsenkarzinomen an der Nase, parasternal und an der Stirn sowie Nachweis eines gut differenzierten Spinalioms an der rechten Schläfe. Diagnose: multiple Talgdrüsenkarzinome im Rahmen eines Muir-Torre-Syndroms bei einer CLL. Diskussion: Das Muir-Torre-Syndrom ist ein seltenes (Inzidenz 1:1000000), autosomal dominant vererbtes, familiäres oder sporadisch auftretendes cancer-Syndrom, welches durch multiple Talgdrüsenkarzinome, Keratoakanthome und viszerale Neoplasien gekennzeichnet ist. Äthiologisch wird eine Mutation des Gens hMSH2 mit folgender Störung der DNA-Mismatch-Reparatur angenommen. Des Weiteren wird auch eine Demaskierung eines latenten Tumor-Syndroms unter langzeitiger immunsuppressiver Therapie diskutiert. Assoziierte viszerale Tumoren beinhalten gastrointestinale Neoplasien (61%), genitale Tumoren (22%) sowie Tumoren der Brust, Lymphome, Leukämien, Bronchialkarzinome, Chondrosarkome und Speicheldrüsentumoren. Hauttumore können metasowie synchron mit visceralen Neoplasien auftreten. Histologisch sind zystische Talgdrüsenneoplasien spezifisch für das MTS, immunhistochemisch lässt sich ein Verlust der Expression von MLH-2 und MSH-1 nachweisen. Eine frühzeitige Diagnose des MTS ist im Sinne einer frühzeitigen Veranlassung von onkologischen Vorsorgemaßnahmen (dermatologisches Screening, Koloskopie, Gynäkologie) essentiell.