Presence of immunoglobulin E-expressing antibody-secreting cells in the dermis close to bullous pemphigoid lesions.

Antibody-secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed.

Tofacitinib, a suppressor of NOD2 expression, is a potential treatment for Blau syndrome.

Introduction: Blau syndrome is a rare autosomal dominant autoinflammatory granulomatous disease caused by a mutation in the gene. It is characterized by a clinical trial of granulomatous dermatitis, arthritis, and uveitis. Tofacitinib is a pan Janus kinase (JAK) inhibitor used for treatment of Blau syndrome and idiopathic sarcoidosis.

Similarities and differences in autoinflammatory diseases with urticarial rash, cryopyrin-associated periodic syndrome and Schnitzler syndrome.

Cryopyrin-associated periodic syndromes (CAPS) and Schnitzler syndrome (SchS) are autoinflammatory diseases that present with urticaria-like rashes. CAPS is characterized by periodic or persistent systemic inflammation caused by the dysfunction of the NLRP3 gene. With the advent of IL-1-targeted therapies, the prognosis of CAPS has improved remarkably.

Decreased peripheral basophil counts in urticaria and mouse model of oxazolone-induced hypersensitivity, the latter suggesting basopenia reflecting migration to skin.

A decrease in the number of basophils in the peripheral blood, or basopenia, has been noted, reflecting the activity of chronic spontaneous urticaria (CSU). Infiltration of basophils into the skin has also been reported, but the mechanism of basopenia in CSU has not been clarified. The phenomenon of basopenia during the active phase of urticaria was confirmed, and basophil numbers increased following symptom improvement in 15 out of 17 patients treated with omalizumab and in 13 of 15 patients treated with antihistamines.

Potential Benefits of TNF Targeting Therapy in Blau Syndrome, a NOD2-Associated Systemic Autoinflammatory Granulomatosis.

Blau syndrome is a systemic autoinflammatory granulomatous disease caused by mutations in the nucleotide-binding oligomerization domain 2 () gene. NOD2 is an intracellular pathogen recognition receptor. Upon binding to muramyl dipeptide (MDP), NOD2 activates the NF-κB pathway, leading to the upregulation of proinflammatory cytokines.

The Potential Role of Basophils in Urticaria.

Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an anti-human IgE antibody that traps IgE and prevents its binding to high-affinity IgE receptors, is effective in treating urticaria. We recently experienced a case of urticaria refractory to antihistamine therapy in which the peripheral-blood basophil count responded to omalizumab therapy and its withdrawal.

A New Era with the Development of Cytokine-Based Therapy for Pruritus.

Pruritus is a common dermatological condition and negatively impacts QOL. Persistent pruritus and excessive scratching behavior can lead to the itch-scratch cycle that exacerbates inflammatory skin diseases. Conventional antipruritic drugs, such as antihistamines, corticosteroids, or anticonvulsants, are sometimes insufficient.

Refractory serum immunoglobulin M elevation during anti-interleukin (IL)-1- or IL-6-targeted treatment in four patients with Schnitzler syndrome.

Schnitzler syndrome is characterized by chronic urticarial rash, neutrophilic dermal infiltrate, recurrent fever, bone pain, elevated C-reactive protein, and neutrophilic leukocytosis. The pathophysiology of Schnitzler syndrome is unknown, but it is considered to be an acquired form of an autoinflammatory disease because of the resemblance to clinical phenotypes of cryopyrin-associated periodic syndrome, in which a gain-of-function mutation in NLRP3 causes overexpression of interleukin (IL)-1β. Schnitzler syndrome is generally accompanied by a monoclonal immunoglobulin (Ig)M gammopathy with a long-term risk of lymphoproliferation that is possibly associated with an MYD88 mutation.

Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials.

Atopic dermatitis (AD) is an inflammatory skin disease arising from a complex interplay of genetic, immune, and environmental factors. The development and successful marketing of the anti-IL-4/IL-13 monoclonal antibody, dupilumab, and the topical nonsteroidal phosphodiesterase 4 (PDE4) inhibitor, crisaborole, as well as the Janus kinase (JAK) inhibitor, delgocitinib, have brought hope for developing new therapeutic agents. The efficacy of these treatments contributes to our understanding of the pathophysiology of AD.