Primary cicatricial alopecia (PCA) is a group of intractable and uncommon hair loss disorders characterized by permanent hair follicle destruction. The pathogenesis of PCA is still not fully understood, and no evidence-based treatment has been established. For patients, permanent hair loss may cause mental stress and their quality of life is markedly reduced. PCA is classified into 3 groups based on the most representative pathological finding of scalp biopsy samples : lymphocytic, neutrophilic and mixed. In this session, representative types of PCA will be discussed based on immunological aspects. For example, frontal fibrosing alopecia may be caused by autoimmune attack on the bulge area. In order to establish an effective therapy, investigation of the pathogenesis of PCA is required.
Hereditary hair diseases are largely divided into polygenic diseases, such as alopecia areata and androgenetic alopecia, and monogenic diseases, which are generally caused by mutations in one gene. Monogenic diseases are further classified into non-syndromic forms, which exhibit only hair symptoms, and syndromic forms in which hair symptoms appear as a part of a syndrome. The latter forms are composed of more than 200 distinct diseases, some of which are known to cause certain immune abnormalities. The causative genes for hereditary hair diseases with immunopathy play important roles not only in hair follicle morphogenesis and development, but also in the maintenance of immune systems and epidermal barrier functions.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but extremely severe and life-threatening diseases. The common causes are medications and infections such as Mycoplasma pneumoniae. SJS/TEN patients present rapidly developing macular exanthema or flat atypical targets in a symmetrical distribution. The buccal, genital and ocular mucosa are involved in most cases. Although the pathomechanisms are not well understood, recent studies have made advancements. SJS/TEN is characterized by necrotic changes in the epidermis and mucosal epithelium due to the death of epidermal cells and mucosal epithelial cells. Although keratinocytes have been suggested to die via apoptosis, our recent study revealed that necroptosis, programmed necrosis, also leads to keratinocyte death in SJS/TEN. Recently, guidelines for SJS/TEN were announced, and improvement of the clinical outcomes of SJS/TEN is expected.
There are currently no biologics approved for the treatment of systemic sclerosis (SSc) , but recent clinical trials and case series studies have suggested that fresolimumab (antibody against TGF-β1, β2, and β3) , tocilizumab (anti-IL-6 receptor antibody) , and rituximab (anti-CD20 antibody) have therapeutic effects for skin sclerosis and/or interstitial lung disease associated with SSc. The clinical efficacy of fresolimumab confirmed the conventional idea that TGF-β plays a central role in the development of tissue fibrosis in SSc. A phase II clinical trial of tocilizumab revealed potential therapeutic effects for skin sclerosis and preventive effects against interstitial lung disease exacerbation in SSc. At this time, a phase III clinical trial of tocilizumab against SSc is ongoing. The majority of case series regarding rituximab have demonstrated favorable effects for skin sclerosis and interstitial lung disease in SSc. An investigator-initiated clinical trial of rituximab against skin sclerosis of SSc is ongoing in Japan. As the clinical efficacy of biologics improves our understanding of the disease pathogenesis, further clinical studies of biologics will promote the development of pathogenesis-based treatments for SSc.
Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity skin reaction caused by T cells reactive to contact allergens, including metals, such as nickel and cobalt, and numerous chemical contact sensitizers termed haptens. Priming of T cells requires the maturation of antigen-presenting dendritic cells (DCs) by activation through innate immune pattern-recognition receptors. However, the innate immune mechanisms by which structurally varied haptens are sensed by and activate DCs are unclear. We recently reported that priming of hapten-specific T cells requires signaling through the IL-1R1-MyD88 pathway triggered by IL-1 released from hapten-stimulated DCs. Chemical contact sensitizers can trigger the activation of spleen tyrosine kinase (Syk) through immunoreceptor tyrosine-based activation motifs (ITAM) . Syk activation induces both CARD9/BCL10-dependent pro-IL-1 synthesis and ROS-dependent NLRP3 inflammasome activation, leading to the secretion of bioactive IL-1α and IL-1β by DCs. Thus, our study revealed an innate immune mechanism essential for contact sensitization to chemical allergens.
Many cytokines, including IL-4, function in the pathogenesis of atopic dermatitis. New molecular target therapies, such as biologics and small molecule inhibitors, are emerging to block these cytokines. Recently, dupilumab, an anti-IL-4Ra antibody, became available. Dupilumab, when used as a single agent, significantly improved the Investigator Global Assessment (IGA) score and increased the number of patients who meet the criterion for EASI-75 compared to the placebo. When used concomitantly with steroid ointment, dupilumab remained highly effective for at least one year. Nemolizumab, an anti-IL-31R antibody, significantly improved pruritus associated with atopic dermatitis in a phase II trial. Topical therapies are also under development. Several phosphodiesterase 4 (PDE4) inhibitors, such as crisaborole, OPA-15406, and E6005, are also promising topical agents. Tofacitinib and JTE-052, which are JAK kinase inhibitors, were also effective in phase II trials, and further clinical trials are expected.
We performed patch tests for contact dermatitis patients and selected Japanese standard allergens (JSA) as a result of a clinical study. However, we are unable to buy the previous allergens. It became possible to purchase the allergens as medicines from 2015, and many dermatologists are now able to perform patch tests. However, the previous positive ratio of JSA and the new ratio must be compared. We found that the positive ratio of metal allergens, specifically gold sodium thiosulfate, increased. Therefore, we investigated gold sensitization among patients who continued to exhibit positive reactions for a long period. We will report the positive ratio of the JSA in the future.
In daily clinical practice, guidance for skin care is important to maintain skin homeostasis for patients with skin dryness (e.g. asteatosis or atopic dermatitis) . As bathing habits change over time, we conducted a questionnaire survey to clarify the bathing habits of patients with skin dryness. This questionnaire had specific questions about body washing methods, bathing habits, and usage of moisturizers. This survey revealed the improper use of liquid detergents and hard washcloths. Although, the small number of subjects and lack of evaluation for the control group were limitations, our results will help form guidelines for patients with skin dryness accompanying asteatosis and atopic dermatitis.
We report a 57-year-old woman who developed allergic contact dermatitis from the temple tips and nose pad of her spectacles. 2-Ethylhexyl-4-methoxycinnamate (brand name Parsol MCX®, ultraviolet absorber) is a common component of sunscreens that often causes photo allergic contact dermatitis. There were two characteristic features in our case : spectacles and sunscreen not being the causative product ; the patch test, but not photo patch test, was positive. With this compound, the patch test was positive, while the photopatch test was negative. In addition, the positive findings of the patch test were comparable between UV-irradiated and non-irradiated trans compounds, although the ratio of cis to trans compounds was approximately 1 : 2. Thus, the patient was diagnosed as ACD, not PACD. This is the first report of allergic contact dermatitis due to 2-ethylhexyl-4-methoxycinnamate contained in spectacles for daily use. An ultraviolet absorber is often used to prevent deterioration from ultraviolet rays. An increase in similar cases in the future is expected.
The patient was a 22-year-old woman who exhibited oral allergy syndrome and/or food-dependent exercise-induced anaphylaxis upon ingestion of several types of fish and a beauty drink containing fish collagen peptide. She tested positive for the specific IgE (CAP FEIA) of many types of fish. On the prick test, she was strongly positive for all fish, fish products, and a beauty drink containing fish collagen and fish collagen peptide, the main component. Using an ELISA method, we diagnosed the allergen component of our patient as fish collagen and not parvalbumin, which is the major allergen from fish. The collagen peptide has a domestic animal origin and fish origin, and as an industrial raw material, is used as a powder and water solution. As the collagen peptide is included extensively in food and health drinks as well as in cosmetics, caution is necessary for patients with fish allergy.