The human microbiome in immunobullous disorders and lichen planus.

For several decades, there has been a significant growth in the incidence of autoimmune diseases. Studies indicate that genetic factors may not be the only trigger for disease development and that dysbiosis of the microbiome may be another mechanism involved in the pathogenesis of autoimmune diseases. The role of the microbiome in the development of common skin disorders such as psoriasis, atopic dermatitis, acne and rosacea is increasingly well understood. However, few studies have focused on lichen planus and the rare acquired immunobullous diseases, both mucocutaneous groups of disorders linked to skin, oral and gut microbiomes. This review provides an insight into the current understanding of how the microbiome may contribute to the development of autoimmunity and to the maintenance and exacerbation of acquired immunobullous and lichenoid diseases. These mechanisms may have implications for future preventive and therapeutic approaches.

[Wells syndrome misdiagnosed as bacterial cellulitis]. / Syndrome de Wells mimant une cellulite bactérienne : un piège diagnostique et thérapeutique.

Wells syndrome (WS), also called eosinophilic cellulitis is a rare inflammatory skin disease with about 200 cases reports in the literature. It is part of eosinophilic dermatoses and presents a diagnostic challenge. We report a case of WS presenting as bacterial cellulitis. A 59 year-old woman was referred to our department with a 10-day history of a rapidly extending erysipelatoid rash of the left upper limb, non-responding to oral antibiotics. Upon physical examination, erythema with swelling and blisters were found on the left upper limb with urticarial-like lesions on the breast, the belly and on the inner thighs. The patient was admitted with presumed bacterial cellulitis and was treated with intravenous ampicillin. Blood count showed raised eosinophils (2050/ul) along with a biological inflammatory syndrome. Biopsies were performed on both bullous and urticarial-like lesions showing perivascular and interstitial inflammatory infiltrate, made essentially of eosinophils with flame figures. The diagnosis of WS was made and the patient received local and oral corticosteroids (0,5mg/kg/d) with good evolution. The rarity and clinical manifestations of WS makes it sometimes difficult to differentiate between a WS and a bacterial cellulitis. However, biological and histological findings can help the clinician make the differential diagnosis between these two diseases for a better management.

Punched-out erosions with scalloped borders: Group A Streptococcal pustulosis.

We present a case of an infant with severe atopic dermatitis infected with Streptococcus pyogenes who presented with pustules, honey-colored crusts, and punched-out erosions with scalloped borders mimicking eczema herpeticum or eczema coxsackium. We draw attention to this case to highlight the similar clinical appearance between bacterial and viral infections in the setting of atopic dermatitis and the importance of a broad workup and coverage while awaiting results.

The microbiome of the "sterile" pustules in palmoplantar pustulosis.

The skin microbiome influences skin pathophysiology. Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by infectious-like pustules on the palms and soles. These pustules are thought to be sterile because bacterial cultures obtained from the pustules are negative. However, culture methods are limited in their ability to identify all bacteria on the skin. We hypothesized that the "sterile" pustules of PPP do not lack bacteria, but rather contain a microbiome. To test this hypothesis, we identified bacteria in "sterile" pustules using non-culture methods. We conducted Sanger and 16S rRNA sequencing using primers specific to the V1-V2 region in PPP-pustulovesicles (PVs) (n = 43) and pompholyx vesicle fluids (n = 15). Sanger sequencing identified some Staphylococcus, Propionibacterium, Streptococcus and Pyrinomonas species in PPP-PVs but failed to identify any bacteria in most of the pompholyx vesicles. 16S rRNA sequencing of PPP-PVs indicated the presence of a microbiome that included various phyla, including Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. At the genus level, smokers had higher levels of Staphylococcus in PPP-PVs compared with non-smokers. These results indicate that a microbiome exists in "sterile" pustules of PPP and that PPP smokers had higher levels of Staphylococcus in pustules. It is therefore necessary to reconsider the pathogenesis of PPP from the perspective of the microbiome.

MRSA in dermatology inpatients with a vesiculobullous disorder.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged worldwide as a major nosocomial pathogen that causes notable morbidity and mortality, especially in vesiculobullous disorders. To study the prevalence of MRSA among patients with autoimmune bullous and drug-induced vesiculobullous disorders and elucidate its predisposing factors and associated mortality, we conducted a prospective, descriptive, 1-year study of all vesiculobullous patients admitted to a tertiary-care center. The prevalence of MRSA in this study was high (32.6%); MRSA constituted 55.8% of all bacterial isolates. All MRSA isolates were resistant to cloxacillin, oxacillin, and cefoxitin; all isolates (100%) were sensitive to vancomycin and linezolid; and 79.1% of isolates (34 patients) were sensitive to amikacin, an inexpensive and readily available antibiotic.

A distinct cutaneous microbiota profile in autoimmune bullous disease patients.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease in Europe. As both the incidence of the disease and the relative proportion of the elderly population continue to rise, it represents a significant medical burden. Whereas some progress has been achieved in defining genetic risk factors for autoimmune blistering diseases, no environmental agent has been conclusively identified. Emerging evidence suggests that host immunity may influence the skin microbiota, while the latter modulates cutaneous immunity. Nevertheless, the relationship between skin microbial communities and autoimmune bullous disease has yet to be studied in humans. Here, we aim to characterise and compare the skin microbiome of patients with BP and healthy, age-matched controls at numerous body sites. Similar to what has been shown in healthy controls, the composition of skin microbiota in patients with BP appears to be very divergent and site specific. Microbial phylum abundances differ between perilesional sites of patients with BP and the same anatomic locations of control patients. A distinct cutaneous microbiota profile, which correlates with BP, further strengthens the significance of commensal-host interaction on our immune system. Moreover, these results raise the possibility that the cutaneous microbiome may contribute to the pathogenesis of BP, with important implications for the treatment of this disease.

Vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease.

BACKGROUND: The diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications. METHODS: We present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM. RESULTS: All four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms. CONCLUSIONS: It is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease.

Subcorneal pustular dermatosis associated with Coccidioides immitis.

Coccidioidomycosis (AKA "Valley fever") is a primary pulmonary infection via airborne spores released from coccidioides immitis in the soil. Reactive cutaneous eruptions resulting from the pulmonary infection are difficult to diagnose because skin biopsies do not contain the organism. We present an adolescent male with primary pulmonary C.immitis infection manifesting with biopsy proven subcorneal pustular dermatosis. Serological studies revealed increasingly positive titers for coccidioidomycosis and symptoms resolved promptly following initiation of systemic antifungal therapy. Our unique case presentation illustrates subcorneal pustular dermatosis as a reactive eruption owing to primary pulmonary coccidioidomycosis. An association between the two conditions warrants further investigation.