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PubMed2026

Causal Relationships Between Oral Microbiota and Inflammatory Skin Diseases.

INTRODUCTION AND AIMS: The oral microbiome has been increasingly linked to systemic inflammation and immune dysregulation, but whether specific oral bacteria causally contribute to inflammatory skin diseases remains unclear due to confounding and reverse causation. This study aimed to assess the causal effects of 43 oral microbiota taxa on the risk of five inflammatory skin diseases using a Mendelian randomization (MR) approach. METHODS: We performed a two-sample MR analysis using genetic instruments for oral microbiota derived from publicly available genome-wide association studies and outcome data from the FinnGen consortium. Causal effects of oral taxa on systemic lupus erythematosus, vitiligo, pemphigus, localized scleroderma, and dermatitis herpetiformis were estimated. The inverse-variance weighted method served as the primary analysis, complemented by sensitivity analyses to evaluate horizontal pleiotropy, heterogeneity, and reverse causality. RESULTS: MR analyses identified several putative causal associations between oral microbiota and inflammatory skin diseases. Genus Granulicatella and an unknown Streptococcus species (ASV0009) showed causal effects on systemic lupus erythematosus. Family Lachnospiraceae_[XIV] and an unknown Rothia species (ASV0016) were associated with vitiligo. Five oral microbiota taxa demonstrated causal associations with pemphigus. Actinomyces species micronuciformis was linked to localized scleroderma. Order Fusobacteriales and an unknown Neisseria species (ASV0004) were associated with dermatitis herpetiformis. No significant heterogeneity or horizontal pleiotropy was detected in sensitivity analyses. CONCLUSION: This MR study provides genetic evidence supporting a causal role of specific oral bacteria in the development of several inflammatory skin diseases, highlighting the oral microbiome as a potential contributor to cutaneous autoimmunity and inflammation. CLINICAL RELEVANCE: Our findings highlight the putative role of the oral microbiome as a plausible candidate for mechanistic and clinical investigations into the prevention or adjunctive management of selected inflammatory skin diseases. However, oral hygiene improvement, targeted antimicrobials, and other microbiota-directed interventions were not directly tested in this MR study and remain hypothetical strategies requiring validation in experimental and clinical studies.

Humans↗
PubMed1979

LETS protein in normal and pathological human oral epithelium.

The distribution of LETS protein in human oral mucosa was studied by indirect immunofluorescence. Normal epithelium showed surface staining. Intracellular staining occurred in epithelial cell cytoplasm in lichen planus and pemphigoid. Surface staining was absent in discoid lupus erythematosus. In pemphigus, intercellular staining was seen near areas of acantholysis.

Acantholysis↗
PubMed1982

Induced pemphigus.

The reports of induced pemphigus have multiplied over the last 10 years. Several heterogeneous factors, such as drugs (penicillamine, pyritinol, captopril, rifampicin, etc.), physical agents (burns, UV, and ionizing radiation) and viruses, can play an inducing role. Usually, the disease is preceded by prodromal, non-specific lesions. The full-blown stage shows features of pemphigus foliaceus, erythematosus or herpetiformis. Histologically, acantholytic splits mostly occur at the highest malpighian layers. Intercellular antibodies and frequently concomitant other auto-antibodies are found in the serum, the titre of the former usually being low and unrelated to the severity or course of the disease. The biological progress is variable and ranges from rapidly and definitively healing cases (induced pemphigus proper) to others which, in spite of the elimination of the inducing factor, self perpetuate just like true pemphigus (triggered pemphigus). Pathogenic hypotheses are based on the act that some inducing factors can alter the antigen distribution on keratinocyte membranes and/or interfere with immune surveillance by impairing T-suppressor cells.

Antibodies↗
PubMed2002

Immunoablative high-dose cyclophosphamide without stem cell rescue in pemphigus foliaceus.

BACKGROUND: There is growing evidence that immunoablative high-dose cyclophosphamide without stem cell rescue is effective and safe in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, aplastic anemia, and more recently pemphigus vulgaris. METHODS: We report a 51-year-old patient with severe pemphigus foliaceus, which was recalcitrant to multiple medical regimes. The patient presented with multiple thick hyperpigmented and scaly, ill-defined plaques on the face. In addition, she had multiple superficial erosions and crusts on her scalp, thorax, upper and lower extremities. The patient also had a few discrete intact flaccid bullae. A skin biopsy and direct immunofluorescence was consistent with pemphigus foliaceus. The patient's circulating pemphigus autoantibodies were present at a titer of 1 : 2560. The patient received immunoablative high-dose cyclophosphamide (50 mg/kg/day) for 4 consecutive days, and tolerated the regime well. RESULTS: Approximately 3 months after therapy, the skin lesions had healed and her prednisone, which had been as high as 80 mg daily, was tapered to 30 mg daily. In addition, her circulating autoantibodies decreased after treatment. Nearly 10 months after treatment, the patient did relapse. However, her disease was less severe and more easily managed with lower doses of immunosuppressive therapy. CONCLUSION: This case contributes to the growing evidence of high-dose cyclophosphamide's efficacy without stem cell rescue in recalcitrant autoimmune diseases, including pemphigus foliaceus.

Cyclophosphamide↗
PubMed1975

Cutaneous immunopathology: recent observations.

Immunofluorescent studies are currently being done on patients with pemphigus, pemphigoid, dermatitis, lupus erythematosus and its variants, the cutaneous prophyrias, scarring alopecia, erosive mouth lesions, light-sensitive disorders, and cutaneous vasculitis. In this paper I shall review some of the recent advances in immunopathology and report the results that have been obtained in our laboratory.

Alopecia↗
PubMed2004

Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) affects 50% of long-term bone marrow transplant survivors and remains a cause of major long-term morbidity in these patients despite aggressive therapy. Extracorporeal photochemotherapy (ECP), considered as an effective treatment for patients with erythrodermic cutaneous T-cell lymphoma (CTCL), has recently been used successfully in the treatment of GvHD. One of the most intriguing aspects of ECP is its ability to induce two apparently opposite effects: activation of the immune system against neoplastic cells (as in CTCL) and downregulation of the activity of T-cell clones in autoimmune diseases (as in systemic sclerosis, systemic lupus erythematosus and pemphigus vulgaris) and autoallogeneic immune responses (as in GvHD and allograft rejection). Only a better and more complete understanding of the various mechanisms involved will enable this interesting new therapy to be made more effective and selective.

Apoptosis↗