Journal of Dermatology最新文献

Advances in next-generation sequencing have facilitated the identification of disease-associated genes for a significant proportion of genetic skin diseases, thereby integrating genetic diagnosis into standard medical care. In Japan, the list of genetic diseases for which genetic diagnosis is available under national health insurance is expanding every year. Since misinterpretation of results of genetic analyses can lead to incorrect genetic counseling, the need for physicians to have a thorough knowledge of genetics is growing massively.

A common challenge in genetic diagnosis is determining whether multiple heterozygous variations detected in the proband are restricted to a single allele or are present in different alleles. This challenge is called “phasing” and typically arises when genomic DNA from the proband's parents is not available. Natsuga presents a comprehensive review of phasing, a critical method for addressing this challenge.

It is becoming clear that a variety of genetic factors underlie common diseases such as atopic dermatitis and psoriasis. Akiyama provides an update on the genetic basis of pustular psoriasis, which is thought to have a particularly strong genetic component associated with inflammatory responses.

There are still some rare diseases for which the genetic cause has not been identified, even with the latest various genetic analysis methods, including next-generation sequencing. To identify a novel disease and a novel genetic, epigenetic or yet unknown genomic cause, it is necessary to accumulate as many cases of the disease as possible. For this purpose, careful description of skin lesions by descriptive dermatology and systematic search for analogous cases is important. Kubo described the history of the discovery of Nagashima-type palmoplantar keratosis from the identification of the disease to the identification of the disease-causing variants in SERPINB7. This record will be useful for future attempts to identify a new independent disease and its pathogenetic factors.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is widely used to distinguish between necrotizing fasciitis and cellulitis. However, LRINEC scores are not as sensitive or specific as initially reported, possibly due to differences in patient backgrounds in different countries. Here, we examined the validity of LRINEC scores in Japanese patients. We also investigated the possibility of developing a new scoring system. Patients with necrotizing fasciitis (n = 56) and cellulitis (n = 209) were retrospectively evaluated. The data were split into training (n = 199) and validation (n = 66) datasets. A logistic regression analysis was used to calculate the C-statistics of the LRINEC scores. A new equation was formulated using logistic regression analysis with an appropriate variable selection (Laboratory Risk Indicator for Necrotizing Fasciitis for Japanese Patients [J-LRINEC] score). The J-LRINEC score had a C-statistic of 0.9683, sensitivity of 91.4%, and specificity of 84.8%. The LRINEC score had a C-statistic of 0.914 and specificity of 96%; however, its usefulness was limited by its sensitivity of 68.9%. Our results suggest that the LRINEC score is valid for Japanese patients; however, the J-LRINEC score showed higher sensitivity and specificity, suggesting that it may be a useful tool for differentiating cellulitis from necrotizing fasciitis among Japanese patients.

Drug-induced hypersensitivity syndrome (DIHS) is one of the severe drug eruptions accompanied by fever and multiple organ dysfunction, and it is induced by a relatively limited range of drugs, including anticonvulsants. A distinctive feature of this condition is its association with the reactivation of herpes viruses, particularly human herpesvirus 6. The pathogenesis involves two key factors: drug allergy and herpesvirus reactivation. DIHS is often challenging to diagnose in its early stages, and its clinical course varies widely, ranging from relatively mild to life-threatening cases. Additionally, unexpected complications, such as autoimmune diseases, may occur during the convalescent phase. As a result, diagnosing, treating, and predicting the prognosis of DIHS remain complex issues. In response to these challenges, the Ministry of Health, Labour and Welfare Study Group on Severe Erythema Multiforme has taken the lead in developing new guidelines for the management of DIHS. These guidelines aim to support clinical practice by providing up-to-date, evidence-based information on the diagnosis, treatment, and prognosis of DIHS.

The association between psoriasis and streptococcal infection has been widely explored in both children and adults. However, the exact impact of Streptococcus pharyngeal infection on the course of psoriasis is not fully comprehended. This study explored the impact of Streptococcus pharyngeal infection on psoriasis and investigated the effectiveness of systemic antibiotic therapy in conjunction with standard topical treatment for psoriatic patients with concomitant streptococcal throat infection. The research involved 115 patients with mild-to-moderate psoriasis, clinically assessed using the Psoriasis Area and Severity Index (PASI). Patients with active streptococcal infection were administered adjunctive systemic antibiotic therapy along with standard local treatment for psoriasis, while psoriasis patients without evidence of infection received the local topical treatment only. Streptococcal infections were more common in psoriasis patients compared to healthy controls. A group of psoriasis patients with active streptococcal throat infections, treated with antibiotics in addition to standard topical psoriasis therapy, did not show any difference in PASI score reduction compared to those without evidence of active infection. While our study did not show a statistically significant reduction in PASI scores in psoriasis patients with streptococcal throat infections treated with antibiotics, it highlights the complex interaction between infection and psoriasis. Larger studies with longer follow-up may better clarify this relationship, contributing to stronger evidence for or against the use of antibiotics in managing psoriasis triggered by streptococcal infections.

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1, leading to loss or dysfunction of type-VII collagen (C7), a protein essential for skin stability. Clinically, patients suffer from severe skin blistering, chronic or recurrent wounds, and scarring, which predispose to early onset of aggressive squamous cell carcinoma. Previous studies showed that RDEB-keratinocytes (RDEB-KC) express high levels of matrix-metalloproteinase 9 (MMP-9), a molecule known to play a crucial role in wound chronification if dysregulated. We investigated the potential of diacerein, a small molecule that interferes with the MMP-9 regulatory pathway, to improve wound healing in a 5-year old RDEB patient presenting with chronic, generalized skin involvement unresponsive to previous treatment approaches. Upon 4 weeks of topical therapy applied to the patient's back, parents reported a nearly complete wound closure and a significant increase in quality of life. We also provide evidence that diacerein treatment of patient keratinocytes results in a downregulation of MMP-9 expression, accompanied by a reduction in their ability to degrade a fibrinogen matrix. These data characterize diacerein as a potential candidate for improving wound healing in RDEB through its impact on inflammatory as well as epithelial cells.

A 51-year-old Indian man presented with a 2-month history of foot ulcers causing pain on exertion. Examination revealed two shallow, oval ulcers on the right dorsal foot with central eschars (Figure 1a). Inspection of the surrounding skin showed atrophic scarring, suggesting previously healed lesions. The patient had no systemic symptoms and no palpable lymphadenopathy. A diagnosis of vasculitis was considered.

The patient presented 3 months later with four new ulcerated and crusted plaques on the right anterior shin (Figure 1b). The previously identified lesions on the right foot had resolved. A skin biopsy of one of the new lesions was performed.

Histology revealed widespread epidermal and dermal necrosis with central ulceration. In the dermis, histiocytes, eosinophils, and infiltrates of atypical lymphocytes were found in an angiocentric pattern (Figure 1c). Lymphocytes invading the vessel walls had led to angiodestruction. Immunohistochemical investigations showed that CD2, CD3, CD4, CD5 and CD7 were positive. Additionally, CD30 and CD8 were focally positive (Figure 1d).

These findings supported a diagnosis of lymphomatoid papulosis (LyP) type E and treatment was commenced with methotrexate. The ulcers resolved within 6 weeks. Treatment was continued for 12 months and no further lesions were observed.

Lymphomatoid papulosis is a rare lymphoproliferative disorder characterized by recurrent papulo-nodular lesions.¹ Despite low disease-specific mortality rates, LyP carries a 20% risk of developing secondary lymphoid malignancy.²

Lymphomatoid type E is an uncommon subtype, making up less than 5% of cases.³ It is characterized clinically by lesions that rapidly break down to form large, eschar-like, necrotic ulcers; the other five subtypes differ as smaller superficial ulceration is seen. Ulceration typically resolves spontaneously within 3–6 weeks leaving atrophic varioliform scarring. Histopathological distinction is based on angiocentric CD30+ and CD8+ atypical infiltrates.⁴ Contradictory to its aggressive presentation, LyP type E has an excellent prognosis; only 5% of patients develop a secondary malignant lymphoma.¹

None declared.

Informed consent was provided by the patient for the use of clinical images.