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Itch is a prominent symptom in many cutaneous disorders, including atopic dermatitis (AD), prurigo nodularis, and psoriasis. Itch is also a common but overlooked concern in patients with hidradenitis suppurativa (HS). Currently, the mechanisms underlying itch in HS remain unclear. To gain a better understanding, we reviewed the literature on pruritus in HS and other itch-predominant disorders, AD, and psoriasis. In HS, psoriasis, and AD, we found that itch often co-localized with pain and occurred more frequently at night. Furthermore, itch was found to negatively affect sleep and increase the risk for comorbid psychiatric disorders in HS, psoriasis, and AD. However, HS-, psoriasis-, and AD-related itch differ in temporality. Itch in AD is often described as chronic, while itch in HS and psoriasis is often described as episodic. HS-associated itch is likely multifactorial, and several mechanisms have been proposed including peripheral sensitization, central sensitization, and neuroinflammation. Prior studies in HS highlight enhanced IgE production and a dense infiltration of mast cells, along with a variety of cytokines and chemokines. Furthermore, alterations in the skin microbiome may contribute to itch in HS. To date, few therapies have been studied to treat itch in HS. Given the efficacy of several biologics and small molecules in treating itch in AD and psoriasis, similar agents may be explored in future HS studies. Alternative therapies to target neurological and psychiatric contributions to itch may include anticonvulsants, cannabinoids, and nonpharmacological treatments. In conclusion, pathomechanisms of itch in HS remain to be fully elucidated. However, we can draw on lessons from other pruritic disorders to begin addressing the symptom of it and identify important questions for future study., (© 2025 Japanese Dermatological Association.)

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo-type AD developing BP after nemolizumab administration. A 62-year-old man with prurigo-type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient's serum anti-BP180-NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high-dose PSL, new blisters continued to develop, with a rapid elevation of anti-BP180-NC16a antibodies to 6930 U/mL. Adding high-dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti-IL-4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL-31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL-4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab-exacerbated BP., (© 2024 Japanese Dermatological Association.)

Nemolizumab is an effective treatment for pruritus in atopic dermatitis, but it has a relatively high incidence of cutaneous adverse events (cAEs). To optimize the use of nemolizumab, we investigated the relationship between baseline severity in specific body areas and the frequency of cAEs. Our findings revealed that cases who discontinued treatment with nemolizumab had more severe erythema and edema/papulation on the trunk than those who continued nemolizumab. We also found that the score of excoriation on the trunk tended to be higher. These results indicate that patients with mild severity of eruptions on the trunk at initiation could be suitable for nemolizumab therapy, with the potential for long-term continuation with the control of cAEs., (© 2025 Japanese Dermatological Association.)

This is the English version of the 2024 clinical practice guidelines for the management of atopic dermatitis (AD). AD is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs, such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment, have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In these revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (© 2024 Japanese Dermatological Association.)

Erythroderma is the end-stage condition caused by various inflammatory diseases, presenting with widespread generalized coalesced erythema on the trunk and extremities. Erythroderma is not a disease itself, but rather is a symptom expressing erythrodermic condition, which is frequently associated with inguinal lymphadenopathy, chills, and mild fever. The clinical characteristics include sparing the folds of the trunk and extremities (deck-chair sign), and cobblestone-like disseminated grouping prurigo; however, the deck-chair sign is not specific to papulo-erythroderma (Ofuji disease). Erythroderma is induced by various causes, such as eczema, psoriasis, atopic dermatitis, drug eruption, lymphoma, lichen planus, pityriasis rubra pilaris, autoimmune bullous diseases, graft-versus-host disease, dermatomyositis, internal malignancy, and others. By contrast, it is not uncommon for even thorough investigations to often fail to identify any significant underlying or occult diseases. Such cases are often diagnosed as idiopathic erythroderma. In elderly cases, some regard erythroderma as late-onset atopic dermatitis, even if the patient does not have a history of childhood atopic dermatitis, while others consider it as a distinct condition with immune responses similar to atopic dermatitis. The etiology of erythroderma is suggested to be a Th2-dominant condition with IL-4/IL-13 playing a central role, suggesting that therapies targeting those Th2 molecules may result in sufficient effects. In this review, the characteristics of erythroderma in the elderly and new therapeutic approaches are discussed., (© 2024 Japanese Dermatological Association.)

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)‐4 and IL‐13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL‐31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti‐IL‐4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti‐IL‐31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti‐IL‐13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board‐certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

Papuloerythroderma (PEO) is a representative form of senile erythroderma with an unclear pathogenesis. This study aimed to characterize the T‐cell phenotypes responsible for the pathogenesis of PEO. Cytokine profiles and cutaneous lymphocyte antigen (CLA) expression on circulating T lymphocytes in patients with PEO were simultaneously analyzed using flow cytometry. The patients with PEO showed significantly higher circulating interleukin (IL)‐4‐, IL‐13‐, IL‐22‐, and IL‐31‐producing CD4+ and CD8+ T‐cell levels than healthy subjects. However, their levels significantly decreased after remission of PEO. No difference was observed in the proportions of circulating interferon (IFN)‐γ‐ and IL‐17‐producing CD4+ and CD8+ T cells between the patients with PEO and healthy subjects. In particular, the proportion of circulating IL‐4‐, IL‐13‐, IL‐22‐, and IL‐31‐producing CD4+ and CD8+ T cells was much higher in the CLA+ subset than in the CLA– subset. There was a positive correlation between IL‐13‐, IL‐22‐, and IL‐31‐producing CD4+ T cells and the disease severity score of PEO. Moreover, a positive correlation was also observed between the proportion of IL‐22‐ or IL‐31‐producing cells and circulating IL‐13‐producing cells in both CD4+ and CD8+ T cells, and approximately 50% of both IL‐22‐ and IL‐31‐producing CD4+ and CD8+ T cells coproduced IL‐13. IL‐13/IL‐22/IL‐31 skewing within the skin‐homing T‐cell population may be involved in the pathogenesis of PEO. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is treated with immunosuppressants. However, long‐term use of immunosuppressants may cause toxicity and severe side‐effects. To confirm the long‐term efficacy and safety of clonal mesenchymal stem cell therapy, we performed investigator‐initiated clinical trials and long‐term observation in five adult patients with moderate to severe atopic dermatitis that was refractory to conventional treatments. The clinical response assessment values such as Eczema Area and Severity Index (EASI) improved significantly at 16 weeks, and 80% (4/5) of the patients achieved EASI‐50 after one or two treatment cycles. Patients were observed for long‐term efficacy and safety for an average of 38 weeks (range, 16–86) and showed no serious side‐effects. Among the cytokines tested, CCL‐17, interleukin (IL)‐13, and IL‐22 significantly decreased at the end‐point of the five participants, two patients who maintained good clinical response over 84 weeks showed increased IL‐17 cytokine levels in the blood. [ABSTRACT FROM AUTHOR]

Prurigo lesions in atopic dermatitis are intractable. This single-center, retrospective study examined dupilumab's clinical effects on intractable prurigo. Twenty adult atopic dermatitis patients (12 with prurigo, eight without) were administrated dupilumab. Its effects on itching and disease severity were examined with Numerical Rating Scale-Itch (NRS-I), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores; body surface areas (BSA); and thymus- and activation-regulated chemokine (TARC), total immunoglobulin (Ig)E, and eosinophil levels. NRS-I scores, EASI scores, TARC levels, and total IgE levels before dupilumab treatment were not statistically different between the prurigo and non-prurigo groups. With dupilumab treatment, NRS-I scores, EASI scores, IGA scores, BSA, TARC levels, and total IgE levels were significantly reduced from baseline in both groups at 1-2 months and onward, but skin symptom improvement in the prurigo group was slower than in the non-prurigo group, as evidenced by significantly higher EASI scores, BSA, and TARC levels at several time points during the 12 months of dupilumab treatment. Prurigo patients were slower in EASI-50 achievement and significantly lower in EASI-90 achievement at 12 months than non-prurigo patients. Adherence to dupilumab was not different, but total equivalent amounts of concomitant therapeutic agents (corticosteroids and tacrolimus) used during dupilumab treatment were significantly higher in the prurigo group (median, 56.2 g/week) than in the non-prurigo group (median, 33.7 g/week). There were 2.2 adverse events per patient on average; ocular complaints were most frequent. Dupilumab was effective in treating intractable prurigo, but despite significantly greater concomitant therapeutic agent use, skin symptom improvement was slower in prurigo patients than in non-prurigo patients., (© 2021 Japanese Dermatological Association.)