A M Powell

Topical imiquimod immunotherapy in the management of lentigo maligna

Melanoma in situ of the lentigo maligna (LM) type is a precursor lesion of LM melanoma. It most commonly occurs in elderly individuals, on the head and neck. Although surgical excision is recommended, this may not be practical for large lesions at cosmetically sensitive sites. In addition, histological changes commonly extend beyond the clinical margins of the lesion. This study describes the use of imiquimod 5% cream as topical immunotherapy in the management of lentigo maligna. Twelve patients (average age 63 years, 10 female), of biopsy‐proven facial LM were treated with topical imiquimod, three times a week for 6 weeks. In the absence of an inflammatory response, patients were asked to apply the treatment daily. Seven showed clearance of the LM clinically and histologically. A further three patients showed clearance histologically with persisting pigmentation due to dermal melanin and melanophages. Thus, 10 of 12 patients cleared with no relapse after a median follow‐up of 6 months. Two patients failed to respond to imiquimod and their lesions were treated with surgical excision. Imiquimod was well tolerated, except in three patients who experienced an intense inflammatory response. Two of these also developed secondary infection. Imiquimod 5% cream appears to offer a potential noninvasive method for the treatment of lentigo maligna.

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

Background  Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically.

Collagen XVII/BP180 : a collagenous transmembrane protein and component of the dermoepidermal anchoring complex

Collagen XVII, or BP180, is a collagenous transmembrane protein and a structural component of the dermoepidermal anchoring complex. Molecular studies reveal that it has a globular cytosolic amino‐terminal domain and flexible‐rod extracellular carboxyterminal domain. The extracellular portion of collagen XVII is constitutively shed from the cell surface by ADAMs (proteinases that contain adhesive and metalloprotease domains). Cell biological analyses suggest that collagen XVII functions as a cell–matrix adhesion molecule through stabilization of the hemidesmosome complex. This concept is supported by investigations into human diseases of the dermoepidermal junction, in which collagen XVII is either genetically defective or absent (as in some forms of nonlethal junctional epidermolysis bullosa). Autoantibodies against collagen XVII (BP180) are seen in bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, linear IgA disease, lichen planus pemphigoides and pemphigoid nodularis. In vivo and in vitro studies provide evidence for a pathogenic role of these autoantibodies, and suggest that the serum level and epitope specificity of these antibodies influences disease severity and phenotype. This review summarizes the structural and biological features of collagen XVII and its role in diseases of the basement membrane zone.

Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label study

Background  Infliximab, a mouse–human chimeric monoclonal antibody directed against tumour necrosis factor‐α, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment‐resistant disease or in combination with other antipsoriatic therapies.

Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid

Background  Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a‐specific enzyme‐linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti‐BP180 autoantibodies in BP sera. However, it remains unclear whether the diagnostic potential of the ELISA is equivalent to that of the ‘gold‐standard’ diagnostic technique of immunofluorescence (IF).

Paraneoplastic pemphigus secondary to fludarabine evolving into unusual oral pemphigus vegetans

We report a patient with chronic lymphocytic leukaemia who developed paraneoplastic pemphigus (PNP) soon after the initiation of fludarabine therapy. He presented with severe oral and cutaneous erosions. Initially, he had high titres of circulating autoantibodies as detected by indirect immunofluorescence (IF) on multiple epithelial substrates (normal human skin, monkey oesophagus, and rat bladder) and by desmoglein 1 and 3 enzyme‐linked immunosorbent assays (ELISAs). His oral erosions have subsequently progressed into unusual hyperplastic papillomatous lesions affecting the inner aspect of lips and buccal mucosae, histologically consistent with pemphigus vegetans. Desmoglein 1 antibodies and IF on rat bladder substrate have become negative after 18 months of therapy. Several agents had been initiated to bring the disease under control originally, but a partial remission was achieved and maintained with mycophenolate mofetil and low‐dose prednisolone.

Discoid lupus erythematosus with secondary amyloidosis

Background   Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes.

Pulsed intravenous cyclophosphamide and methylprednisolone therapy in refractory pemphigus

Background  Pemphigus is a rare autoimmune blistering disorder. The mainstay of current treatment is high‐dose oral corticosteroid therapy in combination with a steroid‐sparing agent. Adjuvant therapy is important for disease control and to reduce the iatrogenic effects of oral prednisolone. Pulsed therapy with intravenous methylprednisolone and cyclophosphamide (PPC) has been shown to be an effective treatment but there are currently few data on its use in patients who have failed to respond to conventional immunosuppression.

Lichen planus pemphigoides evolving into pemphigoid nodularis

Lichen planus pemphigoides (LPP) and pemphigoid nodularis are rare clinical variants of bullous pemphigoid (BP), which are characterized by histological findings of lichen planus (LP) and nodular prurigo, respectively, and the finding of linear deposits of IgG and/or C3 at the basement membrane zone in perilesional skin. In both cases bullae may arise at the site of pre‐existing LP‐like or nodular prurigo‐like eruptions, and clinically uninvolved skin. The disease spectrum of LPP and pemphigoid nodularis differs from that of classical BP phenotype, and their presentations are often indolent. LPP may predominantly affect a younger age group and is responsive to standard treatments used in acquired autoimmune bullous diseases, while pemphigoid nodularis is more common in elderly women and is relatively resistant to therapy. We describe a patient who had LPP for nearly two decades and subsequently developed a nodular eruption with a concurrently detected antibullous pemphigoid antigen 2 (BP180) autoantibody. His overall clinicopathological features were indicative of LPP evolving into another BP variant, pemphigoid nodularis.

Incidence of cancer in the context of atopic dermatitis.

or inadequately effective included (for all 13 patients) topical antiseptics, topical antibiotics, and prolonged antibiotic courses. Other prior treatments included systemic retinoids (four patients), cyproterone acetate (three patients), extensive (excluding localized abscess surgery) surgery (three patients) and dapsone (one patient). They received a median of 25 (range 3–57) treatments. Two patients (2 ⁄13) received two courses of treatment during the surveyed period. One of these patients achieved near complete clearance with 57 treatments which was sustained for 3 months and received a second course of 23 treatments with again near complete clearance, again lasting more than 3 months. The second patient received 24 treatments in the first course with moderate clearance which was sustained at 3 months follow-up and then received 19 treatments in the second course with again moderate clearance. Overall, five (5 ⁄13) patients were recorded to have clear or near clear HS at the end of the course, and in four patients this was sustained at 3 months follow-up. Four patients were documented to reach ‘moderate clearance’, and four to show no to ‘minimal’ improvement. Bath PUVA was generally well tolerated in these 13 patients. Adverse effects from the treatment were recorded for two (2 ⁄13) patients and these were erythema and claustrophobia. We could not find previous reports of bath PUVA to treat HS. We used the topical (bathwater) route to administer psoralen when using PUVA for HS on the basis of an unproven consideration that the psoralen concentration in sinus tracts might be higher than after oral administration and so possibly leading to a greater phototoxic response, leading to antimicrobial and anti-inflammatory effects, in and around sinus tracts. Bath PUVA is possibly an effective medical treatment for some people with HS. A randomized controlled study, with outcome measures to include quality of life, and with adequate follow-up, is needed for this, as for most other medical HS treatments. In the meantime, when selecting treatments for HS when common first-line approaches have failed we will continue to consider offering PUVA.