Clinical and Experimental Dermatology

Potluru, Aparna; Barlow, Richard; Pawlik, Olga; Veitch, David; Wernham, Aaron

doi: 10.1093/ced/llaf019pmid: 39776169

Secondary intention healing (SIH) is utilized by various surgical specialties. The formation of granulation tissue is crucial for initiating the healing process, necessitating robust support at this stage. Numerous adjunct therapies are available, with new developments aimed at treating both acute and chronic wounds undergoing SIH. This article continues from Part 1 and examines the efficacy of various adjunct therapies in promoting SIH.

Palaniappan, Vijayasankar; Karthikeyan, Kaliaperumal

doi: 10.1093/ced/llaf048pmid: 39882979

Lichen nitidus (LN) is a rare inflammatory skin condition characterized by small, shiny, flat-topped papules, commonly affecting children and young adults. Its aetiology remains unclear, although immune-mediated pathways are suspected. LN is often asymptomatic, with papules primarily on the trunk, upper limbs and genitalia. Diagnosis relies on characteristic histopathology, notably a ‘claw clutching a ball’ pattern. Although it often resolves spontaneously, LN may present persistently, sometimes requiring topical treatment. This review highlights the clinical, histological and dermoscopic features of LN, discusses variants and associated systemic conditions, and offers guidance for dermatologists in managing this distinct dermatosis.

Li, Jiayang; Jiang, Guan

doi: 10.1093/ced/llaf117pmid: 40066750

Atopic dermatitis (AD) is a persistent inflammatory skin disease marked by intense rash and itching. Traditional treatments for moderate-to-severe AD, such as methotrexate, often cause significant side-effects. Dupilumab, a biologic therapy that inhibits the interleukin (IL)-4 and IL-13 cytokines, presents a safer alternative. A comprehensive literature review corroborates the safety and effectiveness of dupilumab in patients with AD with cancer. However, the current evidence is limited, necessitating further research. Dupilumab’s targeted mechanism, acting on IL-4 and IL-13, may also positively influence the tumour microenvironment, potentially boosting antitumour responses. Future studies should focus on assessing the long-term safety, efficacy and economic viability of dupilumab across larger and more diverse populations to better understand its dual role in managing both cancer and AD.

Fostier, William; Husain, Akhtar; Namini, Shirin; Mathew, Bipin; Holt, Georgie; Memari, Yasin; Davies, Helen; Koh, Gene C C; Nik-Zainal, Serena; Rajan, Neil

doi: 10.1093/ced/llaf064pmid: 39908333

BackgroundCYLD cutaneous syndrome (CCS) is caused by germline heterozygous pathogenic variants in CYLD and results in the progressive formation of cylindromas, spiradenomas or trichoepitheliomas. Malignant cylindroma is a rare skin adnexal tumour occurring in CCS, which can metastasize with lethal outcomes and has limited genomic characterization. BRCA2 loss in CCS is not described and may modulate the cutaneous cancer risk of CCS.ObjectivesTo establish whether BRCA deficiency drives metastatic malignant cylindroma and to report the phenotype of three siblings with digenic inheritance of CYLD and BRCA2 pathogenic variants (PVs), one of whom developed metastatic cylindroma at 28 years old.MethodsA kindred study reporting seven members of a family with CCS was conducted in a tertiary hospital setting within the United Kingdom from April 2021 to February 2023. Clinical phenotype, pathological, radiological and genetic findings and treatment data were ­collected. Whole-genome sequencing of the primary malignant cylindroma occurring in one patient was performed to identify targetable driver mutations and signatures.ResultsMalignant cylindroma arose in one (proband) of the two male siblings with digenic inheritance of BRCA2 (c.5158insT) and CYLD (c.2689-2A>G) pathogenic variants. A further female sibling with digenic inheritance of the same BRCA2 and CYLD PVs developed early breast cancer. Whole-genome sequencing of the primary malignant cylindroma in the affected patient showed loss of heterozygosity of both BRCA2 and CYLD. Bioinformatic analysis confirmed homologous repair deficiency (HRD). These data supported the use of the PARP [poly(ADP-ribose) polymerase] inhibitor rucaparib to target HRD in a non-canonical BRCA-deficient skin cancer.ConclusionsDigenic inheritance of pathogenic variants in cancer-predisposing genes should prompt clinicians to be vigilant for atypical malignant presentations. We demonstrate that rapid whole-genome sequencing can inform the treatment of metastatic malignant cylindroma and identify novel systemic therapies.

Ali, Mona S; El-Sadek, Hala M; Rageh, Mahmoud A

doi: 10.1093/ced/llaf067pmid: 39908337

BackgroundAcanthosis nigricans (AN) is a prevalent dermatological issue with numerous treatment options that are not entirely satisfactory. Topical vitamin D analogues have been found to be effective and safe for treating AN; however, other preparations of vitamin D have not, to the best of our knowledge, been studied yet.ObjectivesTo evaluate the safety and efficacy of intralesional vitamin D3 injection in treating pseudo-AN.MethodsWe enrolled 30 participants who had bilateral pseudo-AN of the neck. Every patient received intralesional vitamin D3 therapy on the right side of the neck and intralesional saline as a control on the left side over the course of four sessions, each spaced 1 week apart. Participants were assessed clinically 1 month after the last treatment session using the Acanthosis Nigricans Area and Severity Index (ANASI) score in addition to dermoscopic examination.ResultsA statistically significant difference in the ANASI score was seen between the treated and control sides after treatment, with the intralesional vitamin D-treated side exhibiting a larger percentage of reduction than the control side. Intralesional vitamin D3 treatment significantly improved dermoscopic features such as cristae cutis, sulci cutis and pigmented dots compared with the placebo treatment.ConclusionsIntralesional vitamin D3 is a safe and effective modality for treating pseudo-AN.

Ramassamy, Sivaranjini; Chandrashekar, Laxmisha; Mathaiyan, Jayanthi; Rajappa, Medha; Devanathan, Reka; Selvarathinam, Sujeevan; Goud, Alladi Charanraj

doi: 10.1093/ced/llaf070pmid: 39920408

BackgroundPolymorphisms in thiopurine methyltransferase (TPMT) are a predominant cause of azathioprine-induced leucopenia in Western countries. The exact role of these polymorphisms in the Indian population with dermatological disorders is uncertain.ObjectivesTo evaluate the frequency of genetic polymorphism of TPMT and its impact on the safety of azathioprine in dermatological disorders.MethodsWe included consecutive patients on azathioprine who were initiated for dermatological disorders from South India. Three TPMT polymorphisms (c.238G>C, c.460G>A and c.719A>G) were assessed. The proportions of adverse events to azathioprine, especially myelosuppression, were compared between those with the wildtype genotype and those with TPMT polymorphisms.ResultsOf the 123 patients (61 male and 62 female, mean age 46 years), 65% had an autoimmune blistering disorder. Adverse events to azathioprine were noted in 25 (20.3%), of whom 16 (13.0%) had myelosuppression and 4 (3.2%) each had hepatotoxicity and gastrointestinal intolerance. TPMT polymorphisms were detected in 13 (10.6%), of whom 5 had experienced adverse events. The polymorphisms could explain 25% (4 of 16) of the cases of leucopenia. The odds of developing leucopenia in patients with TPMT polymorphism were not significant (odds ratio 3.63, 95% confidence interval 0.96–13.6; P = 0.06).ConclusionsThe tested TPMT polymorphisms could not predict the adverse events of azathioprine, particularly the haematological toxicity, in dermatological use among the South Indian population.

Wang, Qin-Xiao; Ye, Qian; Zhou, Kai-Yi; Luo, Si-Yu; Fang, Sheng

doi: 10.1093/ced/llaf081pmid: 39957318

BackgroundPrimary localized cutaneous amyloidosis (PLCA) is a skin-limited disorder characterized histologically by amyloid deposition in the papillary dermis.ObjectivesTo review current treatment strategies and provide an updated perspective on the treatment of PLCA.MethodsWe searched the PubMed, EMBASE and Cochrane Library databases for eligible studies. Studies were divided into those that described nodular amyloidosis (NA) and those that described non-NA. Cohort studies were meta-analysed using a random effects model to evaluate the outcomes of different treatments, while case reports and case series were evaluated using the Mann–Whitney U-test.ResultsOverall, 116 studies involving 534 patients were included. Surgery was the most effective treatment option in patients with NA, with statistically significantly better outcomes compared with other treatments. For the non-NA group, 62 case-level studies (79 patients) and 20 cohort studies (418 patients) were analysed separately. Although there were no statistically significant differences between treatments in the case-level studies, biologic agents and Janus kinase (JAK) inhibitors may be promising treatments for refractory lesions. Among the cohort studies, partial response rates of 100.0%, 100.0%, 97.5%, 96.9% and 94.4% were achieved for transcutaneous electrical nerve stimulation, microneedling, laser therapies, topical therapies and systemic immunosuppressants, respectively; complete response rates of 22.2% and 2.5% were achieved for surgical interventions and laser therapies, respectively.ConclusionsThis study suggests that surgery is the most effective treatment option for NA, and laser therapy is recommended for patients with non-NA. Biologic agents and JAK inhibitors may be promising treatment options for lesions that do not respond to conventional therapies.

Ma, Sheng-Hsiang; Yeh, Cian-Hao; Chen, Tai-Li; Wu, Chen-Yi; Chen, Chih-Chiang

doi: 10.1093/ced/llaf046pmid: 40238828

BackgroundThe long-term sequelae of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are increasingly being recognized. However, few studies have evaluated the long-term risk of cardiovascular diseases in these patients.ObjectivesThis study aimed to investigate the long-term cardiovascular outcomes in survivors of SJS/TEN.MethodsIn total, 2738 SJS/TEN survivors and 2738 propensity-score-matched controls were enrolled from the US Collaborative Network in the TriNetX database. The primary outcome of this study was the development of a major cardiovascular event (MACE). Patients were followed up from 3 months after the index date until the first diagnosis of an outcome event, withdrawal from the database, or 5 January 2025.ResultsWe found that SJS/TEN survivors had a significantly elevated risk of MACE [hazard ratio (HR) 2.13], ischaemic heart disease (HR 1.57), cerebrovascular disease (HR 2.13) and mortality (HR 1.94) compared with the matched healthy controls. Additionally, the association remained significant in most stratifications, including female, different age groups, disease severity (SJS, SJS/TEN overlap syndrome and TEN) and initial hospitalization status.ConclusionsSome potential confounders may not be acquired in the database. In addition, detection bias is another potential source of bias in this study. This study revealed that SJS/TEN survivors have a significantly higher long-term risk of developing MACE. Understanding these sequelae may provide insights for the holistic care of SJS/TEN survivors.

Sinclair, Rodney; Sicinska, Justyna; Bokhari, Laita; Kasprzak, Michal

doi: 10.1093/ced/llaf012pmid: 39774750

BackgroundThe histological hallmark of male androgenetic alopecia (MAGA) is the transformation of terminal follicles into miniaturized secondary vellus follicles. As the volume of the dermal papilla determines the size of the hair bulb and hair fibre diameter, any treatment-induced increase in fibre diameter could be used as a proxy for reversal of hair follicle miniaturization. Although clinical trials with minoxidil topical solution in MAGA do not demonstrate increased fibre diameter, vellus-to-terminal reconversion is shown in a humanized mouse model treated with minoxidil.ObjectivesTo investigate whether low-dose sublingual minoxidil (SLM) increases hair fibre diameter in MAGA.MethodsSerial tattoo-localized phototrichograms were analysed using hair-to-hair (H2H) matching software in 33 patients with MAGA who participated in a 24-week randomized, double-blinded, placebo-controlled, clinical trial with SLM 0.45 mg once daily. Additional data were obtained from 12 participants who had used a placebo and then rolled into a 24-week, open-label, extension study with either once-daily 1.35 mg or 4.05 mg SLM. TrichoLAB (Warsaw, Masovian, Poland) H2H analysis uniquely identified individual hairs and measured hair fibre diameter at baseline and 24 weeks.ResultsAfter 24 weeks, fibre diameter decreased by 2 µm (SD 1) in men receiving placebo. The decrease was most marked in intermediate diameter fibres with a baseline diameter of 40–60 µm. Among men receiving SLM 0.45 mg, 1.35 mg and 4.05 mg, the mean increase in fibre diameter was −2 µm (SD 1 µm), 3 µm (SD 1 µm) and 6 µm (SD 1 µm), respectively. Intermediate-thickness fibres increased the most. H2H matching demonstrated increased diameter in individual fibres.ConclusionsThe effect of SLM on mean fibre diameter was dose dependent. SLM 1.35 mg and 4.05 mg, but not 0.45 mg, significantly increased mean fibre diameter in MAGA (P < 0.05). The diameter increased most in the intermediate and thickest hairs. This increase in fibre diameter infers reversal of follicle miniaturization in MAGA and is consistent with the observation of vellus-to-terminal reconversion shown in a humanized mouse model treated with minoxidil.

Bai, Ruimin; Cheng, Xiaoqing; Yang, Yajie; Zhang, Jian; Tian, Qiong

doi: 10.1093/ced/llaf065pmid: 39938060

BackgroundPsoriasis is a common autoimmune inflammatory disease. Vitamin B6 is crucial for the body’s inflammatory response, yet the relationship between 4-pyridoxic acid (4-PA), pyridoxal 5′-phosphate (PLP) and vitamin B6 turnover (4-PA/PLP) in psoriasis remains unexplored.ObjectivesTo investigate the relationship of 4-PA, PLP and vitamin B6 catabolism with the risk of psoriasis.MethodsThis cross-sectional study analysed records for 7540 participants from the US National Health and Nutrition Examination Survey. Vitamin B6 catabolism was assessed via the serum 4-PA to PLP ratio (4-PA/PLP). The primary outcome was psoriasis, evaluated using weighted univariate and multivariate logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses were performed by age, gender, body mass index (BMI), hypertension, dyslipidaemia and cardiovascular disease.ResultsOf the participants, 208 had psoriasis. After adjusting for confounders, 4-PA levels in the ‘cutoff above’ group were positively associated with psoriasis (OR 1.51, 95% CI 1.03–2.20). Additionally, 4-PA/PLP correlated with an increased psoriasis risk (OR 1.82, 95% CI 1.02–3.26). However, PLP levels did not show a significant association. The positive link between 4-PA/PLP and psoriasis was consistent in individuals with BMI ≥ 25 kg m–² and hypertension, and in those without dyslipidaemia.ConclusionsThe results revealed a significant association between 4-PA and 4-PA/PLP levels in the presence of psoriasis. However, further extensive prospective studies are necessary to establish causality.