Issue: 9, Page: 1161-1162
International Journal of Dermatology
Issue: 1, Page: 46-52
Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly that lacks adequate treatments. To describe our experience using dupilumab in a series of patients with BP. This is a case series of patients from 5 academic centers receiving dupilumab for BP. Patients were eligible if they had a clinical diagnosis of BP confirmed by lesional skin biopsy evaluated by one of more of the following: hematoxylin and eosin staining, direct immunofluorescence, or enzyme-linked immunosorbent assay for BP180 or BP230, or both. We identified 13 patients. Patients were an average age of 76.8 years, and the average duration of BP before dupilumab initiation was 28.8 months (range, 1-60 months). Disease clearance or satisfactory response was achieved in 92.3% (12 of 13) of the patients. Satisfactory response was defined as clinician documentation of disease improvement and patient desire to stay on the medication without documentation of disease clearance. Total clearance of the BP was achieved in 53.8% (7of 13) of patients No adverse events were reported. Include small sample size, lack of a control group, lack of a standardized assessment tool, and lack of standardized safety monitoring. Dupilumab may be an additional treatment for BP, leading to disease clearance or satisfactory response in 92.3% of patients, including in those in whom previous conventional therapy had failed.
Issue: 3, Page: 575-585.e1
Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.
Issue: 1, Page: e54-e56
This is a case report of a 16-year-old girl recently diagnosed with systemic lupus erythematosus (SLE) who presented with multiple blisters on the face, hands, arms, legs, trunk, and vaginal and oral mucosa. Skin biopsy was consistent with bullous SLE (BSLE). Dapsone is often the first-line treatment option for BSLE, but the patient’s history of anemia and leukopenia and long-term immunosuppression requirement for her systemic symptoms raised concerns about dapsone and bone marrow toxicity, especially hemolytic anemia and agranulocytosis. She was started on intravenous immunoglobulin (IVIG), 2 g/kg divided over 3 days, with significant improvement in her cutaneous symptoms. IVIG is a treatment option for BSLE patients in whom agents such as dapsone are contraindicated.
Paraneoplastic pemphigus (PNP) is a fatal autoimmune blistering disease associated with an underlying malignancy. It is a newly recognized blistering disease, which was first recognized in 1990 by Dr Anhalt who described an atypical pemphigus with associated neoplasia. In 2001, Nguyen proposed the term paraneoplastic autoimmune multiorgan syndrome because of the recognition that the condition affects multiple organ systems. PNP presents most frequently between 45 and 70 years old, but it also occurs in children and adolescents. A wide variety of lesions (florid oral mucosal lesions, a generalized polymorphous cutaneous eruption, and pulmonary involvement) may occur in patients with PNP. The earliest and most consistent finding is severe stomatitis. There is a spectrum of at least five clinical variants with different morphology. Similarly, the histological findings are very variable. Investigations to diagnose PNP should include checking for systemic complications (to identify tumor), skin biopsies (for histopathological and immunofluorescence studies), and serum immunological studies. PNP is characterized by the presence of autoantibodies against antigens such as desmoplakin I (250 kD), bullous pemphigoid aniygen I (230 kD), desmoplakin II (210 kD), envoplakin (210 kD), periplakin (190 kD), plectin (500 kD), and a 170 kD protein. Unlike other forms of pemphigus, PNP can affect other types of epithelia, such as gastrointestinal and respiratory tract. Treatment of PNP is difficult, and the best outcomes have been reported with benign neoplasms that have been surgically excised. The first-line treatment is high-dose corticosteroids with the addition of steroid-sparing agents. Treatment failures are often managed with rituximab with or without concomitant intravenous immunoglobulin. In general, the prognosis is poor, not only because of eventual progression of malignant tumors but also because treatment with aggressive immunosuppression therapy often results in infectious complications, which is unfortunately at this time the most common cause of death in PNP.
Issue: 8, Page: 905-914
The purpose of this review is to provide insight and clarification in the quandary of classification and delineate clinical and histological features and pathophysiology of paraneoplastic pemphigus. This is a paraneoplastic disease of epithelial autoimmunity and adhesion originally described by Dr. Anhalt in 1990. Paraneoplastic pemphigus represents only one manifestation of the heterogeneous autoimmune syndrome in which patients, in addition to small airways occlusion, may display a spectrum of at least five clinical variants of the mucocutaneous disease [i.e. pemphigus-like, pemphigoid-like, erythema multiforme-like, graft-versus-host disease-like, and lichen planus-like, termed paraneoplastic autoimmune multiorgan syndrome (PAMS)]. There is a need for the expanded, inclusive classification of diverse mucocutaneous and respiratory presentations of PAMS. Multiple specific effectors of humoral and cellular autoimmunity mediating epithelial damage have been identified. An update of advances in clinical and basic research on PAMS and in management and overall prognosis of PAMS is provided. © 2011 The International Society of Dermatology.
Issue: 5, Page: 1277-1287
Alopecia areata (AA) is a common T cell–mediated disorder with limited therapeutics. A molecular profile of cytokine pathways in AA tissues is lacking. Although studies have focused on T H 1/IFN-γ responses, several observations support a shared genetic background between AA and atopy. We sought to define the AA scalp transcriptome and associated biomarkers with comparisons with atopic dermatitis (AD) and psoriasis. We performed microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples from patients with AA for comparison with normal scalp samples (n = 6). AA gene expression was also compared with samples from patients with lesional or nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a false discovery rate of less than 0.05 were used for differentially expressed genes (DEGs). We established the AA transcriptomes (lesional vs nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many upregulated immune and downregulated hair keratin genes. Equally impressive as upregulation in T H 1/interferon markers ( IFNG and CXCL10/CXCL9 ) were those noted in T H 2 ( IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), T H 9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in T H 17/T H 22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85 ) were significantly suppressed in lesional skin. Greater scalp involvement (>25%) was associated with greater immune and keratin dysregulation and larger abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85 ). Our data associate the AA signature with T H 2, T H 1, IL-23, and IL-9/T H 9 cytokine activation, suggesting consideration of anti-T H 2, anti-T H 1, and anti–IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.
Issue: S1, Page: 118-119
Clinical and Experimental Immunology
This chapter summarizes current diagnostic criteria and expands on the unique clinical, histological features and pathophysiology of the mucocutaneous disease known as paraneoplastic pemphigus or, by the more encompassing term, paraneoplastic autoimmune multiorgan syndrome (PAMS). PAMS is an autoimmune mucocutaneous eruption that occurs in association with benign or malignant neoplasms. We provide insight and clarification that PAMS represents only one manifestation of the heterogeneous autoimmune syndrome in which patients, in addition to small-airway occlusion, may display a spectrum of at least five clinical variants, i.e., pemphigus-like, pemphigoid-like, erythema multiforme-like, graft-versus-host disease-like, and lichen planus-like. Multiple specific effectors of humoral and cellular autoimmunity mediating epithelial damage have been identified. Mucocutaneous lesions in patients with PAMS occur as a result of both humoral and cell-mediated immune mechanisms. Treatment is difficult and PAMS often does not respond to treatment of the underlying malignancy. An update of the advances in management and overall prognosis of PAMS is provided.
Issue: 1, Page: 111-118
High-dose intravenous immunoglobulin (IVIg) is being increasingly utilized as an off-label therapy for a variety of autoimmune and inflammatory conditions across various specialties. Numerous reports have shown that it is an effective treatment for autoimmune skin blistering disorders. Unlike most therapies for blistering disorders, IVIg is not immunosuppressive and has a favorable side effect profile. This has allowed its use to expand dramatically over the last decade. However, due to the rarity and severity of autoimmune skin blistering diseases, well-designed prospective trials are generally lacking. This work highlights major research developments and the best evidence to date regarding the treatment of autoimmune pemphigus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, pemphigoid gestationis, and linear IgA dermatosis with IVIg, providing an update on its efficacy, proposed mechanisms of action, side effect profile, and indications for use. © Informa UK, Ltd.