Pemphigoid diseases affecting the skin

Pemphigoid diseases are a heterogeneous group of subepidermal autoimmune blistering diseases (sAIBD) that are characterized by autoantibodies against different structural proteins of hemidesmosomes in the epidermal basement membrane zone (EBMZ). The group of pemphigoid diseases affecting the skin include various subtypes, such as bullous pemphigoid (BP), nonbullous pemphigoid (NBP), Brunsting-Perry cicatricial pemphigoid, lichen planus pemphigoides (LPP), pemphigoid gestationis (PG), and anti-p200 pemphigoid. Classification of sAIBD subtypes is mainly based on target antigens and/or clinical manifestations. Pathogenesis of pemphigoid diseases is mediated by predominantly IgG autoantibodies against different structural proteins in the EBMZ. Diagnosis is based on a combination of clinical features, an n-serrated linear pattern of immunodepositions along the EBMZ in direct immunofluorescence microscopy and immunoserology. BP is the most common subtype and most frequently affects elderly, the incidence of BP increased substantially in the past decades. The clinical manifestations of pemphigoid diseases are heterogeneous and represent a clinical spectrum. The typical presentation of BP is a severe pruritus with a predominantly cutaneous lesions consisting of tense blisters or vesicles, erythema and urticarial plaques. In NBP blistering is absent, while the pruritus is severe, and erythematous papules, plaques and excoriations may mimick other inflammatory dermatoses. Recommended therapies consists of whole-body application of superpotent topical corticosteroids, or systemic treatment with immunosuppressive or -modulating drugs.</p

Mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is the subgroup of pemphigoid which predominantly affects mucous membranes. Scarring and limited skin involvement are possible. Several subtypes are classified based on clinical symptoms and target antigens, such as ocular mucous membrane pemphigoid, localized vulvar pemphigoid (LVP) and anti-laminin 332 MMP (anti-LN-332 MMP). Autoantibodies are directed against various structural proteins in the epidermal basement membrane zone (EBMZ), with the 180-kD antigen (BP180) as the main target antigen. Other antigens, such as BP230, the heterotrimeric glycoprotein laminin 332 and A6B4 integrin can also be targeted by autoantibodies. Various mucosa can be affected and are histologically characterized as nonkeratinized stratified squamous epithelium. The clinically heterogeneous disease is characterized by erosions and blistering of the oral mucosa (85%), conjunctiva (30-60%), and less frequently, the nasal mucosa (20-40%), esophagus (5-15%), pharyneal (20%) or laryngeal mucosa (5-10%) and anogenital mucosa (25%). Clinical severity is highly variable in the different subtypes of MMP. Previously, the term cicatricial pemphigoid was used for MMP. Progressive scar formation is a severe complication in ocular MMP and anti-LN-332 MMP, but scarring does not occur in all patients with MMP. Patient and doctors delay is frequently seen in MMP because of the heterogeneous clinical presentation and unfamiliarity among clinicians. For an accurate diagnosis, direct immunofluorescence microscopy (DIF) and detection of circulating autoantibodies in serum is essential. The multidisciplinary management and prognosis of MMP depends on the severity and extent of the disease and involves topical corticosteroids and immunomodulatory and immunosuppressive drugs.</p

Breast implant causes allergic contact dermatitis or foreign body reaction?

In this case report we describe a 55-year-old Caucasian female who had developed an itching, erythematous plaque on the right breast seven months after she received a permanent tissue expander. Topical corticosteroids had no effect upon which a capsulectomy was performed and the complaints disappeared

Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases

Introduction: Rituximab (RTX) is a monoclonal antibody targeting CD20, a transmembrane protein expressed on B cells, causing B cell depletion. RTX has shown great efficacy in studies of pemphigus vulgaris, but data of pemphigoid diseases are limited. Objective: To assess the effectiveness and safety of RTX in pemphigoid diseases. Methods: The medical records of 28 patients with pemphigoid diseases that were treated with RTX were reviewed retrospectively. Early and late endpoints, defined according to international consensus, were disease control (DC), partial remission (PR), complete remission (CR), and relapses. Safety was measured by reported adverse events. Results: Patients with bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 14), epidermolysis bullosa acquisita (n = 5), and linear IgA disease (n = 1) were included. Treatment with 500 mg RTX (n = 6) or 1,000 mg RTX (n = 22) was administered on days 1 and 15. Eight patients received additional 500 mg RTX at months 6 and 12. Overall, DC was achieved in 67.9%, PR in 57.1%, and CR in 21.4% of the cases. During follow-up, 66.7% patients relapsed. Repeated treatment with RTX led to remission (PR or CR) in 85.7% of the retreated cases. No significant difference in response between pemphigoid subtypes was found. IgA-dominant cases (n = 5) achieved less DC (20 vs. 81.3%; p = 0.007), less PR (20 vs. 62.5%; p = 0.149), and less CR (0 vs. 18.8%; p = 0.549) compared to IgG-dominant cases (n = 16). Five severe adverse events and three deaths were reported. One death was possibly related to RTX and one death was disease related. Conclusion: RTX can be effective in recalcitrant IgG-dominant pemphigoid diseases, however not in those where IgA is dominant

Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease

Molecular testing in metastatic basal cell carcinoma

Background: Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. Objective: To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC. Methods: Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. Results: In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib. Limitations: In 2 patients there was insufficient qualitative DNA available for genetic analysis. Conclusions: Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value