Bacterial, fungal and parasitic co-infections in leprosy: A scoping review.

BACKGROUND: In leprosy patients, the most commonly reported non-viral co-infections are Tuberculosis, Leishmaniasis, Chromoblastomycosis and Helminths. The presence of a secondary infection is believed to increase the likelihood of leprosy reactions. The purpose of this review was to describe the clinical and epidemiological characteristics of the most reported bacterial, fungal, and parasitic co-infections in leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Following the PRISMA Extension for Scoping Reviews guidelines, a systematic literature search was conducted by two independent reviewers, resulting in the inclusion of 89 studies. For tuberculosis, a total of 211 cases were identified, with a median age of 36 years and male predominance (82%). Leprosy was the initial infection in 89% of cases, 82% of individuals had multibacillary disease, and 17% developed leprosy reactions. For leishmaniasis, 464 cases were identified, with a median age of 44 years and male predominance (83%). Leprosy was the initial infection in 44% of cases, 76% of individuals presented with multibacillary disease, and 18% developed leprosy reactions. Regarding chromoblastomycosis, we identified 19 cases with a median age of 54 years and male predominance (88%). Leprosy was the primary infection in 66% of cases, 70% of individuals had multibacillary disease, and 35% developed leprosy reactions. Additionally, we found 151 cases of co-infection with leprosy and helminths, with a median age of 43 years and male predominance (68%). Leprosy was the primary infection in 66% of cases, and 76% of individuals presented with multibacillary disease, while the occurrence of leprosy reactions varied from 37% to 81% across studies. CONCLUSION: We observed a male-dominated pattern of co-infections among working-age individuals with multibacillary leprosy. Unlike prior studies reporting increased leprosy reactions in chronic viral co-infections, our findings did not indicate any increase among bacterial, fungal, or parasitic co-infections. Rather, co-infections with tuberculosis and leishmaniasis appeared to reduce leprosy reactions.

Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients.

Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, chronic, subepithelial autoimmune blistering diseases (AIBDs) with predominant involvement of mucous membranes that can be sight-threatening and life-threatening. Rituximab (RTX) has demonstrated its efficacy in severe MMP refractory to conventional immunosuppressants in small series that differed in RTX scheme, concomitant therapies, and outcome definitions. In a meta-analysis involving 112 patients with MMP treated with RTX, complete remission (CR) was reported in 70.5% of cases. Herein, we report the largest retrospective monocentric study on RTX efficacy in a series of 109 severe and/or refractory patients with MMP treated with RTX with a median follow-up period of 51.4 months. RTX was administered in association with immunomodulatory drugs (dapsone, salazopyrine) without any other systemic immunosuppressant in 104 patients. The RTX schedule comprised two injections (1 g, 2 weeks apart), repeated every 6 months until CR or failure, with a unique consolidation injection (1 g) after CR. The median survival times to disease control and to CR were 7.1 months and 12.2 months, respectively. The median number of RTX cycles required to achieve CR in 85.3% of patients was two. The larynx was the lesional site that took the longest time to achieve disease control. One year after RTX weaning, CR off RTX was obtained in 68.7% of cases. CR off RTX with only minimum doses of immunomodulatory drugs was achieved in 22.0% of patients. Further, 10.1% of patients were partial responders and 4.6% were non-responders to RTX. Relapse occurred in 38.7% of cases, of whom 91.7% had achieved CR again at the last follow-up. In MMP, CR was achieved in a longer time and after more rituximab cycles than in pemphigus, especially for patients with MMP with anti-type VII collagen reactivity. RTX with concomitant immunomodulatory drugs was not responsible for an unusual proportion of adverse events. This large study confirms that RTX is an effective therapy in patients with severe and/or refractory MMP, corroborating previous findings regarding the effects of RTX on AIBDs such as pemphigus.

UBA1 Variations in Neutrophilic Dermatosis Skin Lesions of Patients With VEXAS Syndrome.

IMPORTANCE: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. OBJECTIVE: To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. RESULTS: All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients. CONCLUSIONS AND RELEVANCE: This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.

Stress and psoriasis.

The links between psoriasis and stress are complex. This article proposes a review of the literature on the relationship between stress and psoriasis. In 31-88% of cases, patients report stress as being a trigger for their psoriasis. There was also a reported higher incidence of psoriasis in subjects who had a stressful event the previous year, suggesting that stress may have a role in triggering the disease in predisposed individuals. Stress is also a consequence of psoriasis outbreaks. Understanding the role of stress makes it appropriate to target stress when proposing treatment to patients with psoriasis. Several controlled studies have demonstrated that relaxation, hypnosis, biofeedback, and behavioral and cognitive stress management therapies have been effective in people with psoriasis.