Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.

The Fas/Fas ligand system triggers the extrinsic apoptotic pathway and is involved in several inflammatory conditions, also at the skin level. The Fas/Fas ligand cell death pathway plays a major role in anoikis, a type of apoptosis characterized by cell detachment. As pemphigus is characterized by loss of cell to cell adhesion, we evaluated the role of anoikis and Fas ligand in this bullous disease. We report that, in suprabasal epidermis from perilesional pemphigus skin, most keratinocytes are apoptotic. Moreover, Fas ligand levels are markedly increased in sera from pemphigus patients, whereas they are undetectable in sera from patients undergoing steroid treatment. Sera from untreated patients but not from patients under steroids induce keratinocyte apoptosis. Pemphigus-sera-induced cell death is partially inhibited by pretreatment with anti-Fas ligand antibodies and by incubation with caspase-8 inhibitor Z-IETD-FMK. Finally, caspase-8 is activated in keratinocytes provided with sera from pemphigus patients, whereas cleavage is partially blocked by pretreatment of sera with anti-Fas ligand antibody. These results suggest that increased Fas ligand in pemphigus sera is responsible for keratinocyte apoptosis, which occurs through the activation of a caspase-8-driven extrinsic apoptotic pathway.

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SummaryBackground Reticular erythematous mucinosis (REM) is an uncommon disease, the nosology and specific characteristics of which are controversial because most reports deal with single cases or small series. Objectives To describe the characteristics of patients with REM regarding demographics, clinical and pathological features, comorbidities, treatment and course. Methods A retrospective and prospective study was conducted on 25 patients diagnosed with REM in the setting of university-affiliated dermatology departments and dermatopathology centres. Results Of the 25 patients with REM, 16 were women (sex ratio 2 : 1) and the mean age was 46 years. The roles of sun exposure and oral contraceptives were ambiguous. Associated diseases included hypertension (n = 4), malignancies (n = 3), autoimmune diseases (n = 3) and Borrelia infection (n = 1). Immunological studies (including serology and direct immunofluorescence) were noncontributory. The response to antimalarial treatment was good in > 80% of cases. Worsening or recurrence of the lesion after treatment discontinuation, or in the course of the disease, occurred in 31% of patients. Conclusions We present the largest REM case series to date. The reticular pattern with involvement of the midline of the chest and back, the predilection for middle-aged women, the controversial relationship with photosensitivity and the possible association with other conditions such as malignancies and thyroid dysfunctions are the main characteristics that makes REM a recognizable disease.

Most of the MMP sera contain IgG and IgA antibodies to the two major bullous pemphigoid antigens, independent of clinical presentation. Thus, in the majority of cases, patients with exclusively gingival pemphigoid lesions do not appear to have a distinct variety of mucous membrane pemphigoid.

Our data confirm that RBE is not a specific IIF substrate for the serological diagnosis of PNP. It remains a sensitive and specific substrate for the detection of anti-DP antibodies, which, in patients with pemphigus vulgaris, are probably caused by an epitope-spreading phenomenon.

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Pemphigus vulgaris (PV) is the most common type of pemphigus. PV pathogenesis is still debated, and treatment remains challenging. We investigated five controversial topics: (1) What are the target antigens in PV? (2) Do desmogleins adequately address PV pathophysiology? (3) How does acantholysis occur in PV? (4) Is PV still a lethal disease? (5) What is the role of rituximab (RTX) in PV treatment? Results from extensive literature searches suggested the following: (1) Target antigens of PV include a variety of molecules and receptors that are not physically compartmentalized within the epidermis. (2) PV is caused by a variety of autoantibodies to keratinocyte self-antigens, which concur to cause blistering by acting synergistically. (3) The concept of apoptolysis distinguishes the unique mechanism of autoantibody-induced keratinocyte damage in PV from other known forms of cell death. (4) PV remains potentially life-threatening largely because of treatment side effects, but it is uncertain which therapies carry the highest likelihood of lethal risk. (5) RTX is a very promising treatment option in patients with widespread recalcitrant or life-threatening PV. RTX's cost is an issue, its long-term side effects are still unknown, and randomized controlled trials are needed to establish the optimal dosing regimen.