Resolution of a Case of Pediatric Pemphigus Vulgaris Treated with Rituximab

Pemphigus vulgaris (PV) is an infrequent autoimmune bullous disease involving the skin and mucous membranes, which is rare in pediatrics. Although the main therapy for childhood PV are steroids, immunosuppressive drugs are often needed to control the disease. We report the case of an 11-year-old Caucasian boy who presented with a 10 months history of PV unresponsive to steroids and to intravenous immunoglobulin. The therapeutic use of rituximab allowed a long-lasting and complete remission. According to a good safe profile and to our case report, as well as the literature, rituximab may be considered an safe and efficacious treatment for PV.</p

Paraneoplastic pemphigus. A trait d’union between dermatology and oncology

Paraneoplastic pemphigus is a rare autoimmune disease of the skin associated with neoplasm. Nowadays, the pathogenesis of paraneoplastic pemphigus is not fully understood. Due to its rarity, various criteria have been proposed for the diagnosis. For this reason, several diagnostic methods have been considered useful for the diagnosis of paraneoplastic pemphigus including indirect immunofluorescence, direct immune of fluorescence, immunoprecipitation,immunoblotting, and enzyme-linked immunosorbent assay (ELISA). However, the polymorphic clinical features and the various results of laboratory tests and pathological evaluation present a challenge for the clinician

Paraneoplastic pemphigus: insight into the autoimmune pathogenesis, clinical features and therapy

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed “paraneoplastic pemphigus”. We included also papers in French, German, and Spanish. We found 613 papers for “paraneoplastic pemphigus”. Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist

Case report: bullous pemphigoid development underlies dystrophic epidermolysis bullosa disease worsening

Autoimmune response to cutaneous basement membrane components superimposed on a genetic skin fragility disease, hereditary epidermolysis bullosa (EB), has been described, but its effects on disease course remain unclear. We report a 69-year-old individual with congenital skin fragility and acral trauma-induced blistering that had suddenly worsened with the onset of severe itch and diffuse spontaneous inflammatory blisters. Next-generation sequencing identified compound heterozygous null and missense COL7A1 mutations, allowing the diagnosis of recessive dystrophic EB. However, the patient’s clinical history prompted us to investigate whether he might have developed a pathological autoimmune response against basement membrane components. Tissue-bound and circulating IgG antibodies to the major bullous pemphigoid (BP) antigen, BP180, were detected in the patient’s skin and serum, respectively, consistent with a diagnosis of BP. Corticosteroid therapy was initiated resulting in remission of BP manifestations. EB patients presenting rapid disease worsening should be investigated for the development of a concomitant autoimmune blistering disease

Environmental factors in autoimmune bullous diseases with focusing on seasonality: new insights

Autoimmune bullous diseases are a heterogeneous group of rare conditions clinically characterized by the presence of blisters and/or erosions on the skin and on the mucous membranes. Practically, they can be divided into two large groups: the pemphigoid group and the pemphigus group, depending on the depth of the autoimmune process on the skin. Family history of autoimmune disease can often be found, and demonstrating that genetic predisposition is crucial in the development of them. Moreover, numerous environmental risk factors, such as solar radiation, drugs and infections, are known. This study aimed to evaluate how seasonality can affect the trend of BP and PV, especially considering the number of hospitalizations recorded over the course of individual months. The total number of hospitalizations in the twelve months of the year was evaluated. Further, blood chemistry assay and, for some patients, enzyme-linked immunosorbent assay were executed in order to evaluate antibodies. Regarding the severity of the disease BPDAI (Bullous Pemphigoid Area Index) and PDAI (Pemphigus Disease Area Index), score systems were used. Results showed a complex interplay between environmental factors such as seasons and autoimmune conditions

Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface

Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3 and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3 from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro, and 2 were pathogenic in a passive transfer model in neonatal mice. The epitopes recognized by the pathogenic antibodies were mapped to the DSG3 extracellular 1 (EC1) and EC2 subdomains, regions involved in cis-adhesive interactions. Using a site-specific serological assay, we found that the cis-adhesive interface on EC1 recognized by the pathogenic antibody PVA224 is the primary target of the autoantibodies present in the serum of PV patients. The autoantibodies isolated used different heavy- and light-chain variable region genes and carried high levels of somatic mutations in complementary-determining regions, consistent with antigenic selection. Remarkably, binding to DSG3 was lost when somatic mutations were reverted to the germline sequence. These findings identify the cis- adhesive interface of DSG3 as the immunodominant region targeted by pathogenic antibodies in PV and indicate that autoreactivity relies on somatic mutations generated in the response to an antigen unrelated to DSG3

Transition from Pemphigus Vulgaris to Pemphigus Foliaceus after Toxic Epidermal Necrolysis

The most frequent subtypes of autoimmune pemphigus are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). They are caused mainly by antibodies against desmoglein (Dsg) 1 and Dsg3. Sera from patients with mucocutaneous PV contain both anti-Dsg1 and anti-Dsg3 autoantibodies, whereas sera from patients with PF have anti-Dsg1 autoantibodies only. The transition from PV to PF has been rarely described in the literature and the mechanism that leads to a shift in autoantibodies profile remains unknown. We report a case of long-standing recalcitrant PV, that showed a transition to PF after the administration of etanercept 50 mg in order to threat toxic epidermal necrolysis (TEN) arisen after rituximab administration