Role of Rituximab in the Treatment of Pemphigus Vulgaris: Patient Selection and Acceptability.

Anti-CD20 monoclonal antibody rituximab is an approved adjuvant treatment, in combination with oral corticosteroids, for patients with pemphigus vulgaris, a severe and potentially life-threatening autoimmune blistering skin disorder. Updated approaches to the management of pemphigus vulgaris support rituximab as a first-line adjuvant treatment to induce remission early in the course of disease; however, its feasibility in the clinical setting is often reduced by a series of limitations, including high cost of this biological drug, physician and patient concern for the risk of adverse reactions, and uncertainty regarding the optimum dosing and schedule of administration. The standard approved rituximab dosages, which are derived from lymphoma protocols, have been recognized to exceed the effective dose required for inducing B cell depletion, since the B cell burden in pemphigus vulgaris is much lower than in lymphoproliferative disorders. To overcome these limitations, recent research has investigated alternative regimens of rituximab, using lower doses of the drug. Moreover, differences in patient and disease characteristics that are highlighted in the literature strongly suggest that therapy should be tailored individually on a case-by-case basis: personalized treatment schedules may be necessary to optimize response to treatment and tolerability in different subjects, with the possibility of repeated infusions for severe forms and in case of relapse. Finally, low-dose regimens of rituximab were suggested to be favorable during the COVID-19 pandemic by providing a lesser degree of immune cell depletion while retaining a sufficient response. In conclusion, the current literature suggests that lower-dose regimens of rituximab are not only tolerable and cost-effective but may also be associated with a positive response in pemphigus vulgaris, comparable to that achieved with higher doses especially in early disease. Further evidence from rigorous clinical trials will be required to optimize lower-dose regimens of RTX and establish their position within the treatment scenario of pemphigus vulgaris.

The Pathological Culprit of Neuropathic Skin Pain in Long COVID-19 Patients: A Case Series.

Cutaneous neurosensory symptoms have become increasingly reported findings in COVID-19; however, these virus-related manifestations are largely overlooked, and their pathology is poorly understood. Moreover, alterations of skin sensibility currently recognize no clear histopathology substrate. The purpose of this study was to provide pathology evidence of neurosensory skin system involvement in COVID-19 patients complaining of subjective neurological symptoms affecting the skin. Out of 142 patients, six long COVID-19 cases complaining of cutaneous subjective neurological symptoms assessed on an NTSS-6 questionnaire underwent histopathological and immunohistochemical analyses of skin areas affected by paroxysmal diffuse burning and itching sensations. Two patients also performed electroneurography examination. The histology investigation showed hypertrophic glomus vascular bodies with hypertrophic S100+ perineural sheath cells and adjacent hypertrophy of the nerve branches associated with increased basophil polysaccharide matrix. Electroneurography revealed disturbances of A-delta and C dermal neuronal fibers. The main limitation of this study consisted of a limited number of skin biopsy samples, requiring further investigation. Histopathology findings are consistent with hypertrophy of nerve endings, suggesting a condition such as "dermal hyperneury", a recently reported small nerve hypertrophy condition affecting sensory C fibers. Such a neuropathic basis could explain dysesthesia experienced by the patients, as previously described in postherpetic neuralgia.

Impact of COVID-19 on patients with atopic dermatitis.

Data on the tolerability and response to biologic therapies for type 2 immune disorders in the context of coronavirus disease 2019 (COVID-19) are currently lacking. Our survey aimed at assessing the adherence of patients to dupilumab therapy and the risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 80 patients with atopic dermatitis treated with dupilumab completed a web-based survey. Of the 80 patients, 7 discontinued dupilumab owing to concerns and difficulties related to COVID-19. Our sample was highly susceptible to viral infection owing to the frequency of risk factors including living in high SARS-CoV-2 burden areas, such as in Northern Italy; having comorbidities, such as asthma, diabetes, and cardiovascular disease; and being of advanced age. Older patients in our sample are particularly exposed to the risk of COVID-19-related cytokine storm, triggered by excessive interleukin-4 production and type 2 immune response. One patient contracted SARS-CoV-2 infection without the progression of COVID-19 despite continuing scheduled dupilumab treatment. Because evidence on the appropriate management of biologic therapy in the setting of COVID-19 is lacking, the collection of clinical data from patients in treatment with dupilumab is a valuable addition to current clinical practice. Our survey provides a contribution to the understanding of the tolerability and response to dupilumab during COVID-19 and suggests a feasible and effective approach to patients being treated with biologics even when social distancing is required.

Cutaneous adverse reactions after COVID-19 vaccines in a cohort of 2740 Italian subjects: An observational study.

An in-depth characterization of the incidence, morphology, and onset of COVID-19-vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID-19 vaccination-related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID-19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine-related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID-19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID-19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID-19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.

Telogen Effluvium after SARS-CoV-2 Infection: A Series of Cases and Possible Pathogenetic Mechanisms.

INTRODUCTION: Physicians have largely studied the cutaneous involvement of coronavirus disease 2019 (COVID-19), but only few reports have focused on telogen effluvium (TE) as a possible sequela of COVID-19. We assessed 14 cases of hair loss occurring after SARS-CoV-2 infection using trichoscopy and trichogram to investigate patterns related to COVID-19. Furthermore, we discussed possible mechanisms involved in COVID-19 TE. CASE PRESENTATION: Fourteen individuals were referred to our post-COVID-19 dermatology office complaining acute hair loss after SARS-CoV-2 infection. Clinical evaluation included pull test, trichoscopy, and trichogram. CO-VID-19 TE occurred after a median of 2 months (range 1-3 months) following SARS-CoV-2 infection. The median duration of hair loss was 5 months (range 1-6 months). Trichoscopy showed variable but typical TE patterns. Trichogram showed different telogen/anagen ratio depending on the interval between onset of hair loss and trichological visit. DISCUSSION/CONCLUSION: Our cases showed TE between 1 and 3 months after the onset of SARS-CoV-2 infection, thus earlier than classic TE. Trichoscopic features and trichogram showed no variations from classic TE. Different pathogenetic mechanisms including pro-inflammatory cytokines and direct viral damage on the hair follicle can be hypothesized; further studies on a larger sample are needed to better understand this condition.