[The main autoimmune bullous diseases]. / Les principales maladies bulleuses auto-immunes.

Autoimmune bullous diseases are disorders in which the immune system mistakenly attacks certain molecules that act as "glue" in the various layers of the skin, leading to the formation of bullae or vesicles. A bulla is a liquid-containing lesion over five millimeters in size on the skin or mucous membranes. It forms due to a loss of cohesion between the epidermis and dermis, or between keratinocytes within the epidermis. Diagnosis is based on biopsies, which show the presence of autoantibodies and the depth of skin detachment. A blood test can be used to identify circulating autoantibodies.

[Local treatments for bullous pemphigoid]. / Les soins locaux dans la pemphigoïde bulleuse.

Bullous pemphigoid affects people who are usually very frail, because they are very old and frequently have neurological co-morbidities. Over the past twenty years, therapeutic management has improved thanks to the application of highly potent corticosteroid-based creams, following a well-established regimen, for several months. Well-conducted nursing care is therefore essential not only to cover wounds, but also to treat the disease. Dedicated nursing time is also an opportunity to provide support to patients, who are often very uncomfortable.

[A rare presentation of kidney allograft intolerance syndrome: Bullous pemphigoid]. / Une présentation rare du syndrome d'intolérance au greffon renal : la pemphigoïde bulleuse.

Bullous pemphigoid is an autoimmune bullous cutaneous disease. We report the case of a 60 year-old male patient whose kidney allograft failed and was on hemodialysis for the previous 16 months. After tapering immunosuppressive medication, he presented simultaneous bullous eruption and kidney allograft intolerance syndrome. Investigation showed a positive BP180 anti-basement membrane zone antibody and skin biopsy was consistent with bullous pemphigoid. The patient was treated with corticotherapy and bullous pemphigoid resolved. The development of new onset diabetes and concerns over long term immunosuppression, halted the decision to continue corticotherapy and the patient underwent graft nephrectomy, with resolution of the kidney allograft intolerance syndrome without recurrence of the bullous disease. The occurrence of bullous pemphigoid in patients with failed renal allograft is rare, with only eleven cases reported in literature. This case illustrates how graft nephrectomy can provide a definitive cure to bullous pemphigoid in this setting.

Radiation-induced bullous pemphigoid after surgery for soft tissue sarcoma: About a rare case.

INTRODUCTION: Radiation therapy may cause a range of side effects of the skin within the irradiated area. Not of all the reactive effects of the skin induced by radiation therapy have to be related to some forms of radiodermatitis, and when non-standard clinical presentations overcome, it may be necessary to undertake appropriate diagnostic tools to not be in trap of wrong diagnosis. CLINICAL CASE DESCRIPTION: A 76 years-old man undertook resection surgery after a neoadjuvant radiation therapy for a soft tissue sarcoma of his groin region. After surgery, he developed an acute skin reaction comparable with a severe form of radiodermatitis. Despite cares, his clinical status got worse. Only skin biopsies guided us to the right diagnosis: it was a form of a bullous pemphigoid induced by radiation therapy. The consequent appropriate treatment was finally resolute. CONCLUSION: These forms have to be recognized in time, to undertake skin biopsies as soon as an evocative clinical presentation appears. The appropriate treatment, which consists in local or systemic corticotherapy, is resolute in most cases.

[Epidermolysis bullosa acquisita with Brunsting-Perry type pemphigoid: Diagnostic and therapeutic difficulties]. / Épidermolyse bulleuse acquise à type de pemphigoïde de Brunsting-Perry : difficultés diagnostiques et thérapeutiques.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare auto-immune blistering disease. We report a case of Brunsting-Perry pemphigoid diagnosed by immunoelectron microscopy (IEM). PATIENTS AND METHODS: A 46-year-old man presented very pruriginous vesicles on the face and neck present for 6 years and which were difficult to diagnose and treat. The appearance of atrophic scars and milium cycts evoked EBA, which was confirmed at IEM. Due to limited involvement of the face and the neck, we conclude on EBA of the Brunsting-Perry pemphigoid variant. Treatment with dapsone produced a favorable outcome. DISCUSSION: Diagnosis of EBA is often difficult. In a case review, Asfour et al. collated 60 cases of Brunsting-Perry pemphigoid. These patients had either anti-collagen VII or anti-BP180 and anti-BP230 antibodies. IEM showed cleavage either under the lamina densa or within the lamina lucida, suggesting that Brunsting-Perry pemphigoid is a subtype of EBA or bullous pemphigoid (BP), depending on the paraclinical elements, and localized to the head and neck. The majority of EBA-like cases required systemic therapy, whereas in the presence of BP antibodies, topical corticosteroids were effective. CONCLUSION: We report a case of EBA of the Brunsting-Perry pemphigoid type, diagnosed by IEM after 6 years of progression. We highlight the diagnostic and nosological difficulties of Brunsting-Perry pemphigoid. Classification of this dermatosis as a subtype of EBA or BP may enable effective adaptation of therapeutic management, which has not as yet been coded.

[Dermatologic toxicities of immune checkpoint inhibitors]. / Toxicités dermatologiques des inhibiteurs de checkpoint immunologiques.

The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment. More than a third of patients are faced with cutaneous adverse events, usually in the form of a maculopapular rash, pruritus or vitiligo (only in patients treated for melanoma). Much more specific dermatologic disorders, however, may occur such as lichenoid reactions, induced psoriasis, sarcoidosis, auto-immune diseases (bullous pemphigoid, dermatomyositis, alopecia areata), acne-like rash, xerostomia, etc. Rigorous dermatological evaluation is thus mandatory in the case of atypical, persistent/recurrent or severe lesions. In this article, we review the incidence and spectrum of dermatologic adverse events reported with immune checkpoint inhibitors. Finally, a management algorithm is proposed.

[Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses]. / Immunité à médiation humorale : vascularites cutanées et maladies bulleuses auto-immunes.

Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses.

[What's new in dermatological treatment?] / Quoi de neuf en thérapeutique dermatologique ?

On a therapeutic point of view, 2017 in dermatology could be summarized in one disease, one pathway and in one number : atopic dermatitis, JAK inhibitors and 23. 2017 will be the year of the first registration of a biologic treatment in atopic dermatitis, dupilumab, with numerous other drugs currently in development. JAK inhibitors show promising results in several difficult-to-treat conditions, such as alopecia areata, vitiligo or atopic dermatitis, but still warrant confirmation in upcoming controlled trials. Monoclonal antibodies targeting IL-23 have confirmed in phase III studies their great efficacy in controlling psoriasis and will be soon available in practice, illustrating well the optimal link between bench side and bed in this emblematic inflammatory dermatological condition.

[Amyopathic dermatomyositis (DM) with anti-MDA5 antibodies, associated with bullous pemphigoid, Sjögren syndrome and gastric MALT lymphoma]. / Dermatomyosite amyopathique avec anticorps anti-MDA-5, associée à une pemphigoïde bulleuse, un syndrome de Sjögren et un lymphome de type MALT.

BACKGROUND: The inflammatory myopathies are a heterogeneous group of muscle diseases and comprise polymyositis, dermatomyositis (DM), myopathies associated with cancers, necrotising myositis and inclusion body myositis. DM occasionally exhibits few or no muscular signs: i.e. hypomyopathic/amyopathic DM. Anti-MDA5 dermatomyositis (DM) is a rare form of dermatomyositis that is frequently amyopathic; the prognosis is linked mainly to pulmonary involvement. PATIENTS AND METHODS: A 69-year-old woman treated for mucosa-associated lymphoid tissue (MALT) gastric lymphoma was referred for a bullous eruption. Based on the investigations performed, a diagnosis was made of bullous pemphigoid. At the same time, amyopathic dermatomyositis was discovered together with interstitial lung disease. Systemic steroids were introduced in combination with rituximab. A favourable outcome was achieved. DISCUSSION: Anti-MDA5 dermatomyositis must be considered systematically in all cases of pulmonary involvement associated with cutaneous signs of dermatomyositis, in which no muscular involvement is generally seen. This condition accounts for up to 7% of DM and carries a severe prognosis due to pulmonary involvement.

Bullous pemphigoid, a dermatosis of the elderly / La pemphigoïde bulleuse, une dermatose du sujet âgé

Bullous pemphigoid, a dermatosis of the elderly. Bullous pemphigoid is the most common autoimmune bullous disease and affects almost exclusively the elderly. Its occurrence is related to the presence of pathogenic autoantibodies directed against structural proteins (BP180 and BP230) of the protein adhesion complex of the dermo-epidermal junction: the hemi-desmosome. Bullous pemphigoid is classically characterized by pruritus and the appearance of blisters on an inflammatory background with a symmetrical topography: thighs, arms and trunk. Blisters eventually break, leading to erosions. Mucosal involvement is rare. Histology of a cutaneous biopsy finds a subepidermal blister containing eosinophils. Direct immunofluorescence confirms the diagnosis by the presence of linear deposits of IgG and C3 along the epidermal basement membrane. The reference treatment is the superpotent topical corticosteroid therapy (clobetasol propionate).

La pemphigoïde bulleuse, une dermatose du sujet âgé. La pemphigoïde bulleuse est la dermatose bulleuse auto-immune la plus fréquente et elle touche quasi exclusivement la personne âgée. Sa survenue est liée à la présence d'autoanticorps pathogènes dirigés contre des protéines de structure (BP180 et BP230) du complexe protéique d'adhésion de la jonction dermo-épidermique : l'hémidesmosome. La pemphigoïde bulleuse se manifeste classiquement par un prurit et l'apparition de bulles sur fond inflammatoire avec une topographie symétrique : cuisses, bras, tronc. Les bulles finissent par se rompre, laissant la place à des érosions. L'atteinte muqueuse est rare. L'histologie d'une biopsie cutanée montre une bulle sous-épidermique contenant des polynucléaires éosinophiles. L'immuno- fluorescence directe affirme le diagnostic par la présence de dépôts linéaires d'immunoglobuline de type G et de C3 le long de la membrane basale épidermique. Le traitement de référence est la corticothérapie locale très forte (propionate de clobétasol).

[Impact of neurological diseases on the prognosis of bullous pemphigoid: A retrospective study of 178 patients]. / Impact pronostique des maladies neurologiques au cours de la pemphigoïde bulleuse : étude rétrospective de 178 cas.

BACKGROUND: Bullous pemphigoid (BP) mainly affects elderly patients. It is often associated with neurological disorders, which constitute a major risk factor of the disease. The aim of our study was to determine whether neurological disorders, particularly dementia, influence outcome and mortality in BP patients. PATIENTS AND METHODS: We conducted a retrospective study of all patients with BP seen in our dermatology department consecutively between 1997 and 2011. Clinical, immunological and therapeutic data, number of relapses and survival status were compared according to the presence at diagnosis of neurological disorders, particularly dementia. RESULTS: Among the 178 patients included, an associated neurological disease was present in 84 (47.2%) and dementia in 43 (24.2%) at the time of diagnosis of BP. Patients with associated dementia were older and had a lower Karnofsky index. Sixty-four patients (37.8%) had had at least one clinical relapse of BP, chiefly within the first 18 months after starting therapy. Coexistent neurological disease was not associated with BP relapse (P=0.55) contrary to an extensive BP phenotype at diagnosis (P=0.008). Coexistent neurological disease and/or dementia were associated with higher mortality (P=0.03 and P<0.001, respectively), but did not modify the type or the total duration of BP treatment. CONCLUSION: A coexistent neurological disease or dementia at the time of diagnosis of BP significantly increase the risk of mortality and shortens the duration of clinical follow-up of patients with BP, thus limiting the analysis of their influence on the outcome of BP itself.

[Pemphigoid gestationis and Turner syndrome; an uncommon association]. / Pemphigoïde de la grossesse et syndrome de Turner ; une association inhabituelle.

The authors report an uncommon case of a pregnant woman with Turner syndrome (TS) whose pregnancy (with favorable outcome) was complicated by a pemphigoid gestationis in third trimester. This case points out that monitoring of these pregnancies is not limited to cardiac monitoring. Prevalence of auto-immune diseases is increased in the TS. Auto-immune dermatoses, such as pemphigoid gestationis, are one of the potential complications during pregnancy and should be known to practitioners.

[What's new in clinical dermatology?]. / Quoi de neuf en dermatologie clinique?

Significant advances have been performed in cutaneous adverse reactions leading to primary prevention strategy and implication of new signaling pathways. Histological features of DRESS and methotrexate toxicity are detailed. New emerging infectious agents are reported including Zika Virus, an arbovirus which can be confused with dengue or chikungunya, a new cowpox virus transmitted by domestic cat leading to lymphadenitis, Spirurina type X larva transmitted in Japan by eating raw squid or fish. Malignancies in pemphigus and pemphigoid are emphasized. Expert recommandations are developped on definitions, diagnosis and disease activity of mucous membrane pemphigoid, bubllous pemphigoid and pemphigus. Psoriasis and cardiometabolic association are discussed. This risk association appears higher in hidradenitis suppurativa, which seems more frequent in patients of African ancestry. IgG4-related disease is an immune mediated entity characterized by fibroinflammatory lesions often misdiagnosed. Pruritus, heat sensations, numbness could be recognized as a small-fiber neuropathy symptoms. Burden impact in common dermatosis is demonstrated and should be integrated in our daily practice.

[Pregnancy-specific dermatoses]. / Dermatoses de la grossesse.

Pregnancy-specific dermatoses include polymorphic eruption of pregnancy, atopic eczema of pregnancy, and pemphigoid gestationis. Intrahepatic cholestasis of pregnancy and impetigo herpetiformis are not real pregnancy-specific dermatoses but they are important to know considering the fetal and maternal risks. Polymorphic eruption of pregnancy is a pruritic disease that usually occurs in primiparous women during the last trimester of pregnancy. Atopic eczema of pregnancy is still controversial as an entity covering conditions with eczematous lesions, prurigo, or folliculitis, and inconstantly associated with a personal history of atopy. Skin biopsy with direct immunofluorescence or search for serum anti-BPAg1 (180kD) NC16a antibodies is mandatory in pruritic dermatoses of pregnancy in order to rule out pemphigoid gestationis. Serum bile salts levels should be tested whenever a generalized pruritus develops during pregnancy in order to rule out intrahepatic cholestasis.

[What's new in clinical dermatology?]. / Quoi de neuf en dermatologie clinique?

Dermatoses have been better characterized as hypochromic vitiligo in subjects with dark skin or the acquired racquet nails associated with hyperparathyroidism. The innate immunity has a central role in the new classification of auto inflammatory diseases, neutrophilic dermatoses, neutrophilic urticaria or pseudo-neutrophilic urticaria. Comorbidities have been studied e.g. cardiovascular co morbidities for psoriasis, IBD associated with hidradenitis suppurativa or neurological disorders associated with pemphigoid. Bullous pemphigoid could be renamed as cutaneous pemphigoid, it can be induced by drugs especially gliptins. Genetic predispositions are analyzed in auto inflammatory diseases, psoriasis (HLA), drug eruptions (HLA or cytokines). Telaprevir often induces rashes, which can be severe but other treatments against hepatitis C as interferon can also induce debilitating rashes, some eligible for drug tolerance induction. European guidelines for the definition, classification, diagnosis of chronic spontaneous urticaria have been published. Severe cutaneous adverse drug reactions may be associated with severe systemic symptoms such as organ involvement in AGEP or the occurrence of a shock in DRESS. Allover Europe, there is now an epidemic of contact allergies to methylisothiazolinone (MIT), contained in cosmetics, wet wipes but also in paints. MIT should be tested at 2.000 ppm in water, included in the standard series for patch tests. Its role has to be evoked in any case localized on the face or hand, airborne or generalized eczema. Among infectious diseases, skin manifestations due to Parvovirus have been specified, a febrile rash can be related to dengue infection or to Zika virus.

[Small cell lung cancer associated with paraneoplastic bullous pemphigoid]. / Cancer pulmonaire à petites cellules associé à une pemphigoïde bulleuse paranéoplasique.

The broncho-pulmonary small cell carcinoma is the most common cancer provider paraneoplastic syndrome especially neurological and endocrine but also cutaneous syndrome. Paraneoplastic dermatosis do not result from a direct extension of cancer and are not metastases, but their presence is suggestive of an underlying tumor. The evolution of the dermatosis is parallel to that of cancer: treating cancer results in the regression of cutaneous manifestations. We report an observation of a 44-year-old smoker, who was hospitalized for a tissue excavated process associated with bullous dermatosis. The transmural puncture biopsy finds small cell carcinoma. The skin biopsy objective bullous pemphigoid. The evolution under chemotherapy was marked regression of bullous lesions and the patient died later after metastatic extension. Cutaneous paraneoplastic syndrome appears only in a minority of cancer patients, but its recognition is very important for early diagnosis.

[Choriocarcinoma: a hidden face of pemphigoid gestationis]. / Le choriocarcinome: une face cachée de la pemphigoïde gestationnelle.

Gestationis pemphigoid is an autoimmune subepidermal blistering dermatosis occurring predominantly in pregnancy, more seldom in early puerperium, and exceptionally in post-abortion. The association of gestationis pemphigoid with choriocarcinoma is extremely rare. We report this association in a patient of 35 years in which the diagnosis of gestationis pemphigoid was made on clinical, histological and immunological criteria, and the one of choriocarcinoma was made on clinical, biological radiological and histological criteria. Through this article, we put the item on this association reported for the first time in post-abortion.

[Autoimmune blistering diseases]. / Les maladies bulleuses auto-immunes.

Autoimmune blistering diseases are characterized by the production of pathogenic autoantibodies that are responsible for the formation of epidermal blisters. Major advances in the understanding of the pathogenesis of these disorders have allowed the development of new therapeutic agents. Recent epidemiologic data showed that bullous pemphigoid mainly affects elderly patients. Bullous pemphigoid is often associated with degenerative neurologic disorders. A major increase in the incidence of bullous pemphigoid has been observed in France. Treatment of bullous pemphigoid is mainly based on superpotent topical corticosteroids. The role of desmosomal proteins has been demonstrated in the initiation, propagation and persistence of the autoimmune response in pemphigus. Several studies have shown a correlation between anti-desmoglein antibody titers and disease activity. Pemphigus susceptibility genes have been identified. Oral corticosteroids remain the mainstay of pemphigus treatment. Dramatic and long-lasting improvement has been recently obtained with rituximab in recalcitrant types of pemphigus. Other autoimmune junctional blistering diseases are rare entities, whose prognosis can be severe. Their diagnosis has been improved by the use of new immunological assays and immunoelectronic microscopy. Immunosupressants are widely used in severe types in order to prevent mucosal sequelae.

[Anti-p200 pemphigoid: Remission under mycophenolate mofetil (Cellcept®)]. / Pemphigoïde anti-p200: rémission sous mycophénolate mofétil (Cellcept®).

BACKGROUND: Anti-p200 pemphigoid is a recently described autoimmune subepidermal bullous dermatosis characterized by its target antigen and the associated anatomoclinical picture. The treatment is not as yet well defined. PATIENT AND METHODS: A 73-year-old man consulted for a pruritic bullous eruption with buccal involvement. Direct immunofluorescence revealed linear deposits of IgG and C3 at the dermal-epidermal junction. Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. A diagnosis of bullous pemphigoid was suspected. After an unfavourable clinical outcome under clobetasol and then prednisolone and methotrexate, other immunological tests were performed. Indirect immunofluorescence on NaCl-cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting showed antibodies directed against a 200-kDa antigen on a dermal extract. A diagnosis of anti-p200 pemphigoid was made. The patient was treated with dapsone combined with prednisolone. Seventy-two hours later, treatment was stopped due to hepatic cytolysis related to immunoallergic hepatitis. Treatment with mycophenolate mofetil was then initiated and resulted in complete remission, which persisted at seven months. DISCUSSION: The diagnosis of anti-p200 pemphigoid was made on the basis of a set of clinical and immunological factors. Anti-p200 pemphigoid differs from standard bullous pemphigoid in terms of more frequent cephalic, acral and mucous membrane involvement, as well as a greater degree of miliary scarring. There was no eosinophilia. Elisa screening for anti-BP180 and anti-BP230 antibodies was negative. Immunoblotting showed antibodies directed against a 200kDa protein on dermal extract. The treatment is not well defined, even if dapsone appears to be the most effective therapy. To our knowledge, our patient is the first to be successfully treated with mycophenolate mofetil. CONCLUSION: Treatment of anti-p200 pemphigoid is difficult. In our case, treatment by mycophenolate mofetil was effective and could offer an alternative to dapsone.