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Chaninan Kositkuljorn,1 Suthinee Rutnin,1 Teerapong Rattananukrom,1 Teeraya Puavilai,2 Burana Khiankaew,3 Paisarn Boonsakan,3 Wimolsiri Iamsumang1 1Division of Dermatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Hematology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Wimolsiri Iamsumang, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Rajthevi, Bangkok, 10400, Thailand, Tel +662-201-1141, Fax +662-201-1211, Email i.wimolsiri@hotmail.comAbstract: Methotrexate-related lymphoproliferative disorders (MTX-LPDs) are immunodeficiency diseases following methotrexate (MTX) administration, mainly occurring in rheumatoid arthritis patients. Although uncommon, MTX-LPDs have been reported in some patients with psoriasis, dermatomyositis, and cutaneous T-cell lymphoma (CTCL) who received MTX. Granulomatous mycosis fungoides (GMF) is a rare subtype of cutaneous T-cell lymphoma, where MTX is one of the treatment options in recalcitrant cases. Herein, we report a case of a 72-year-old female patient with GMF who additionally developed cutaneous Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) during MTX treatment. According to the 5th edition of the WHO classification of Haematolymphoid Tumors (WHO-HAEM), this condition is currently categorized as “lymphoma arising in immunodeficiency/dysregulation”. In this article, we also reviewed published literature on cutaneous MTX-LPDs in the setting of CTCL. This entity should be considered in cases of new, atypical skin nodules and/or plaques in CTCL patients receiving long-term MTX treatment.Keywords: cutaneous T-cell lymphoma, granulomatous mycosis fungoides, methotrexate, methotrexate-related lymphoproliferative disorders

Nawara Sakpuwadol, Kasama Tejapira, Chaninan Kositkuljorn, Cherrin Pomsoong, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat Suchonwanit, Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand, Tel +66-2-2011141, Fax +66-2-201-1211 ext 4, Email poonkiat@hotmail.comBackground: Female pattern hair loss (FPHL) is the most common hair loss disorder in women that can be classified into three patterns, including Ludwig, Olsen, and Hamilton-Norwood subtypes. Information regarding the comparison of demographics, clinical characteristics, and associated comorbidities among subtypes of FPHL is scarce and contradictory.Objective: To evaluate and compare the epidemiology, clinical manifestations, and comorbid conditions of FPHL subtypes and determine their associated factors.Methods: This retrospective study included patients who were diagnosed with FPHL between January 2000 and November 2021. Participants were classified into three subtypes, namely Ludwig, Olsen, and Hamilton-Norwood, and were statistically compared. Variables significantly associated with each FPHL subtype were identified using multivariable multinomial logistic regression analysis.Results: Among the 519 patients with FPHL, the Ludwig subtype was the most prevalent (51.1%), followed by the Olsen (32.9%) and Hamilton-Norwood (16%) subtypes. The Hamilton-Norwood subtype revealed significantly higher frequencies of early disease onset (61.4%), menstrual irregularity (22.9%), polycystic ovary syndrome (PCOS, 18.1%), and seborrhea (30.1%) but lower frequencies of overweight (24.1%) and type 2 diabetes mellitus (DM, 2.4%). Multivariable multinomial regression analysis demonstrated that the Hamilton-Norwood subtype was a predictor for early disease onset and PCOS compared to Ludwig (early onset: odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.39– 4.22, P = 0.02; PCOS: OR = 2.02, 95% CI = 1.55– 4.84, P = 0.03), and Olsen (early onset: OR = 1.89, 95% CI = 1.03– 3.92, P = 0.04; PCOS: OR = 2.24, 95% CI = 1.89– 5.31, P = 0.01). In contrast, the Hamilton-Norwood pattern was at decreased risk for type 2 DM compared to Ludwig (OR = 0.51, 95% CI = 0.03– 0.82, P = 0.02), and Olsen (OR = 0.68, 95% CI = 0.04– 0.79, P = 0.03).Conclusion: The Ludwig pattern was found to be the most prevalent FPHL subtype among Thai patients. Moreover, the Hamilton-Norwood subtype was associated with early disease onset and PCOS, whereas the Ludwig and Olsen subtypes were associated with type 2 DM.Keywords: AGA, androgenetic alopecia, comorbidity, FPHL, non-scarring alopecia, subtype

Kumutnart Chanprapaph, Cherrin Pomsoong, Chaninan Kositkuljorn, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat SuchonwanitDivision of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, ThailandTel +66-2-2011141Fax +66-2-201-1211 Ext 4Email poonkiat@hotmail.comIntroduction: Intramuscular corticosteroids (IMC) have gained popularity for the treatment of severe alopecia areata (AA) in recent years; however, evidence on their efficacy and safety is still limited.Objective: To evaluate the efficacy, relapse rate, and tolerability of IMC in the treatment of AA, as well as factors associated with treatment outcomes.Methods: Time-to-event analysis was performed on patients with severe, extensive, or rapidly progressive AA receiving IMC. The IMC regimen comprised triamcinolone acetonide 20– 40 mg/mL injected every 4– 6 weeks. The evaluated outcomes included initial (25% regrowth), significant (75% regrowth), and complete hair regrowth (100% regrowth). Relapse and adverse events were also noted. Factors associated with treatment outcomes and relapse were analyzed using the Cox proportional hazards model.Results: A total of 101 patients were eligible for analysis. Significant hair regrowth was obtained in 80.2% of the patients (n = 81), in a median time of 3.4 months (95% confidence interval [CI] = 2.9– 4.4). Complete hair regrowth was achieved in 48.5% of the subjects (n = 49), and relapse was observed in 47.5% (n = 48). Acneiform eruption was the most common adverse effect. Multivariable analysis revealed that nail involvement was a negative predictor of significant hair regrowth (adjusted hazard ratio [HR] = 0.04, 95% CI = 0.01– 0.55; P = 0.015), whereas duration of AA longer than 6 months was associated with disease recurrence (adjusted HR = 4.02, 95% CI = 1.52– 4.66; P = 0.005).Conclusion: This study demonstrated the efficacy and safety of IMC in the treatment of severe or active AA; however, the relapse rate remained relatively high after discontinuation of the therapy. Nail involvement was a negative predictor of significant hair regrowth, while disease duration longer than 6 months predicted AA relapse.Keywords: acute diffuse and total alopecia, alopecia totalis, alopecia universalis, hair loss, injection, systemic

Kumutnart Chanprapaph, Thipprapai Mahasaksiri, Chaninan Kositkuljorn, Kanchana Leerunyakul, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat SuchonwanitDivision of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, ThailandTel +66-2-2011141Fax +66-2-201-1211 ext 4Email poonkiat@hotmail.comBackground: Increased rates of autoimmune diseases (ADs) have been reported in association with alopecia areata (AA); however, the risk factors for coexisting ADs in AA patients have been poorly investigated.Objective: To evaluate the prevalence and factors associated with AD comorbidities in patients with AA.Methods: This case–control study included patients diagnosed with AA between January 2000 and March 2020. Individuals with AA, both with and without concomitant ADs, were statistically compared. Variables significantly associated with coexisting ADs were identified using univariate and multivariate logistic regression analyses. Multinomial logistic regression analysis was performed to identify the specific risk factors for each concomitant AD.Results: Among the 615 patients with AA, comorbid ADs were found in 76 (12.4%). Autoimmune thyroid disease (AITD) exhibited the highest frequency (n = 42, 6.8%), followed by vitiligo (n = 15, 2.4%), and systemic lupus erythematosus (SLE) (n = 12, 2.0%). Logistic regression analyses revealed that female sex (odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.24– 4.82; P = 0.011), nail abnormalities (OR = 2.49, 95% CI = 1.14– 5.46; P = 0.023), and atopic diseases (OR = 1.98, 95% CI = 1.09– 2.43; P < 0.001) were significantly associated with coexisting ADs. Regarding each concomitant AD, nail abnormalities were an associated factor for AITD (OR = 4.65, 95% CI = 1.96– 7.24; P = 0.01), whereas coexisting atopic diseases were demonstrated as a predictor of vitiligo (OR = 2.48, 95% CI = 1.43– 4.58; P = 0.02). Female sex (OR = 1.61, 95% CI = 1.18– 4.27; P = 0.04) and family history of AD (OR = 1.85, 95% CI = 1.26– 4.19; P = 0.03) were predictors of SLE.Conclusion: This study suggests that female AA patients with nail abnormalities and atopic diseases have increased rates of AD comorbidities. A thorough review of systems for associated factors can help physicians screen for concomitant ADs.Keywords: AA, comorbidity, hair loss, non-scarring alopecia, predictor, systemic disorders

Thipprapai Mahasaksiri, Chaninan Kositkuljorn, Tanaporn Anuntrangsee, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat SuchonwanitDivision of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, ThailandTel +66 2-2011141Fax +66 2-201-1211 Ext 4Email poonkiat@hotmail.comAbstract: Treatment of extensive or recalcitrant alopecia areata (AA) is a major clinical challenge. Even after thorough investigation of several medications, its treatment outcomes have remained unsatisfactory. While there is no US Food and Drug Administration-approved medication for AA yet, topical immunotherapy has been a well-documented treatment option. Dinitrochlorobenzene, squaric acid dibutylester, and diphenylcyclopropenone are three substances that have demonstrated efficacy in the treatment of extensive or recalcitrant AA. Despite being commonly used, the mechanism underlying topical immunotherapy is not well-elucidated and a wide range of clinical efficacies have been reported in the literature. The aim of this review was to summarize and update the pharmacology, mechanism of action, therapeutic efficacy, and tolerability of topical immunotherapy in the treatment of AA.Keywords: contact sensitizers, dinitrochlorobenzene, diphencyprone, diphenylcyclopropenone, hair loss, squaric acid dibutylester

Purpose: Sleep disturbances affect human health and contribute to several comorbidities. In men, androgenetic alopecia (AGA) is a common, non-scarring form of hair loss that affects a patient's self-esteem. There are limited data regarding the association between poor sleep quality and male AGA. We aimed to compare the prevalence of sleep abnormalities between male patients with AGA and controls to identify an association between the two conditions., Methods: A case-control study on patients with AGA and age-matched controls was conducted. Participants completed a standardized questionnaire that contained self-evaluated sleep measures, including Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and STOP-BANG questionnaire. Patients with AGA were classified into mild, moderate, and severe subgroups according to the Hamilton-Norwood classification for stratified analyses. Data between groups and among subgroups were compared., Results: Of 446 male participants, 223 (50%) were in the AGA group, and the remainder (50%) were in the control group. Multivariable logistic regression analysis revealed that hypertension (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.16-3.11, p = 0.011) and STOP-BANG score ≥ 5 (OR = 2.05, 95%CI = 1.15-3.66, p = 0.015) were associated with AGA. For subgroup analyses, ordinal logistic regression model showed a significant association between severe AGA and three sleep profiles, namely total sleep time ≤ 6 h (OR = 2.16, 95%CI = 1.02-4.57, p = 0.044), PSQI > 5 (OR = 3.72, 95%CI = 1.42-9.72, p = 0.008), and STOP-BANG score ≥ 5 (OR = 3.01, 95%CI = 1.11-8.13, p = 0.030)., Conclusion: Our findings revealed an association between sleep disturbances and AGA, which may help guide appropriate management in these patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: This study aimed to demonstrate the effects of gender-affirming hormone therapy (GAHT) and gender-affirming procedures on the skin in transgender individuals., Methods: We conducted a cross-sectional study among transgender people. Skin conditions related to GAHT were assessed, including acne (using the Investigator's Global Assessment, IGA), postacne sequelae, melasma, hypertrichosis in androgen-sensitive areas (HAAs) in transgender men (TM) and hirsutism in transgender women (TW) (using the modified Ferriman-Gallwey score, mFG score), and hair loss (using the Hamilton-Norwood and Ludwig scale) at baseline, 6 months after GAHT, and the day on which the questionnaire was completed. Dermatological problems after gender-affirming procedures were evaluated., Results: A total of 159 patients, including 134 TM and 25 TW, were eligible to participate. The median duration of GAHT was 23 and 36 months in TM and TW, respectively. In TM, the median IGA score of facial acne increased from 1 at baseline to 3 after 6 months and decreased to 2 after 2 years of GAHT. The mFG score indicated HAA in all TMs after testosterone treatment. A total of 88.1% of TM had no hair loss before hormone therapy. However, after 2 years of GAHT, 76.1% of TM developed male pattern hair loss (MPHL), and 26.1% of them had moderate-to-severe MPHL. In TW, the median IGA and mFG scores decreased after 3 years of hormone therapy, and the proportion of female pattern hair loss (FPHL) in TW increased to 16% after GAHT. In both groups, the most common skin complication after gender-affirming surgery was hypertrophic scarring., Conclusions: GAHT in TM resulted in acne and MPHL, whereas GAHT in TW caused melasma and FPHL., Competing Interests: No competing financial interests exist., (© Suthinee Rutnin et al. 2023; Published by Mary Ann Liebert, Inc.)

Background: Palmoplantar and periungual warts tend to be recalcitrant. Intralesional immunotherapy can provide high efficacy with additional benefit to distant warts. However, evidence on comparative effects between intralesional immunotherapy with measles, mumps, rubella vaccine (MMR) and tuberculin purified protein derivative (PPD) and roles of dermoscopy in predicting treatment outcomes in palmoplantar/periungual warts is limited., Objectives: The study aimed to compare efficacy and safety of intralesional MMR and PPD injections in treatment of palmoplantar/periungual warts and explore associations between dermoscopic findings and treatment outcomes., Methods: We conducted a double-blind randomized controlled trial involving 40 patients with palmoplantar/periungual warts who were equally assigned to receive MMR or PPD. Intralesional injection was done every 2 weeks until clearance or maximum of 5 treatments., Results: Complete resolution was higher in MMR than PPD group (90.0% vs. 80.0% in index lesion and 81.3% vs. 54.6% in distant lesions, respectively), although the differences were statistically nonsignificant. Dermoscopic findings were not significantly associated with complete resolution. Local swelling, i.e., the most common adverse event, occurred more frequently in PPD (40.0%) than MMR group (10.0%)., Conclusion: This study suggests that intralesional immunotherapy with either MMR or PPD is efficacious in palmoplantar/periungual warts, with MMR showing a trend toward higher clearance and lower adverse events., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Topical corticosteroids (TC) and/or intralesional corticosteroids (IC) are considered first-line treatments for patch-type alopecia areata (AA). However, the efficacies of TC monotherapy, IC monotherapy, and combined topical and intralesional corticosteroids (CC) in patients with AA have never been compared., Objective: To evaluate and compare the efficacy and tolerability of 3 corticosteroid treatments (TC, IC, and CC) in patients with AA., Methods: A study of patients with AA who received TC, IC, or CC was conducted. Outcomes including initial hair regrowth (25% regrowth), significant hair regrowth (>80% regrowth), and adverse events were statistically compared. Cox proportional hazards regression analysis was used to identify factors that influence the treatment response., Results: One hundred and forty-eight patients were eligible for analysis. The response rates of initial and significant hair regrowth were comparable among 3 treatment groups. Multivariate analysis revealed that an AA treatment duration of longer than 6 months was associated with a lower probability of significant hair regrowth. A small proportion of patients experienced adverse effects., Conclusion: The 3 corticosteroid treatment regimens are effective, safe, and show no significant differences in treatment outcomes. However, an AA duration longer than 6 months portends a lack of significant hair regrowth.

Background: Enlarged facial pores are a common cosmetic complaint in practice. Microfocused ultrasound with visualization (MFU-V) and low-degree crosslinked hyaluronic acid filler (L-HA) injection has recently become a popular procedure for skin rejuvenation. The effectiveness of the combined MFU-V and L-HA injection in the treatment of enlarged pores has not been evaluated., Objectives: To compare the efficacy of MFU-V monotherapy (single technique) and MFU-V combined with L-HA injection (combined technique) for the treatment of enlarged facial pores in Asians., Methods: We conducted a randomized, single-blinded, split-face study on participants with enlarged facial pores. Each side of the face was randomly assigned to treatment with one session of single technique or combined technique. Pore volume was objectively measured by an Antera 3D ® system. Subjective assessment was evaluated by one-blinded physician using a pore grading score (0-4). Patients rated the improvement in terms of satisfaction using the visual analog scale (VAS, 0-10)., Results: Forty-six participants completed the study. The mean pore volume of both sides declined with statistical significance at every visit compared to baseline, with the lowest mean at 4 months post-treatment. The combined technique showed a lower mean pore volume than single technique throughout the follow-ups. Physician's subjective evaluation showed no statistically significant difference between the two techniques. The patient satisfaction score showed a similar trend to the mean pore volume, with a statistically significant difference at 4 and 6 months post-treatment., Conclusions: Both techniques are effectively minimize enlarged facial pores. The combined technique resulted in more patient satisfaction., (© 2021 Wiley Periodicals LLC.)

Alopecia areata (AA) is an autoimmune disease of the hair follicles. It is characterized by a well-defined non-scarring alopecic patch or patches that may extend to the entire scalp or lead to total body hair loss. Due to its unpredictable clinical course, AA causes substantial psychological harm. Despite the high prevalence of this disease and extensive research, its exact pathomechanism is unclear, and current treatments have a high relapse rate that has deemed AA incurable. Over the past few decades, researchers have investigated multiple potential factors that may help alleviate its pathogenesis and provide effective treatment. Given its complex immunopathogenesis, AA is considered an autoimmune disease with multiple factors. This review gathers current evidence that emphasizes molecular mechanisms, possible causative etiologies, and targeted immunotherapies for AA. Understanding its underlying mechanisms may shed light on new strategies to effectively manage AA in the future., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Suchonwanit et al.)

Background: Isobutylamido thiazolyl resorcinol (ITR) is a novel anti-tyrosinase recently shown to be effective in the treatment of hyperpigmentation. Low-fluence Q-switched Nd:YAG 1064-nm laser (LFQS) has proven to be effective for various hyperpigmentary conditions. However, there is no study on the efficacy and safety of combined ITR and LFQS treatment., Objectives: To compare the efficacy and safety of combined ITR and LFQS with LFQS monotherapy for facial hyperpigmentation., Materials and Methods: Patients with symmetrical facial hyperpigmentation were treated with five sessions of once weekly LFQS on the whole face. One side was randomly treated with ITR and the other side received a placebo cream for 12 weeks. Patients were followed for 8 weeks after the last laser treatment. Relative lightness index (RL*I), Facial Hyperpigmentation Severity Score on the malar area (FHSS m ), patient satisfaction, recurrence, and adverse events were recorded., Results: Twenty-four patients completed the study. Both sides demonstrated significant reductions of mean RL*I and mean FHSS m from baseline (P < .01). At the 4th week, the ITR-treated side showed more improvement of mean RL*I than the placebo-treated side (62.5% vs 47.3% improvement, P < .05). The mean FHSS m on the ITR-treated was reduced at a significantly higher percentage than the placebo-treated side (54.4% vs 40.2% reduction, P < .05). Partial recurrence was observed on both sides. No serious side effects were noted., Conclusion: Combined ITR and LFQS therapy was more superior than LFQS monotherapy in the treatment of facial hyperpigmentation. ITR may serve as adjuvant for patients with such condition., (© 2020 Wiley Periodicals LLC.)

Background: Ultraviolet (UV) exposure contributes to skin hyperpigmentation. Recently, botulinum neurotoxin type A (BoNT-A) showed a promising protective effect on UVB-induced hyperpigmentation in both in vitro and animal models., Objective: The study aimed to investigate the preventive effect of BoNT-A against UVB-induced hyperpigmentation in human subjects., Materials and Methods: A prospective, double-blinded, randomized controlled trial was performed in 15 healthy participants. Four separate square areas on the abdomen were randomly injected intradermally with different dilutions of BoNT-A (1:2.5, 1:5, 1:7.5) and normal saline (control). Two weeks after injection, hyperpigmented spots were induced by UVB irradiation at the experimental sites. The lightness index and hyperpigmentation scores from blinded physician and participants were evaluated., Results: Fifteen participants completed the study. One week after UVB irradiation, all BoNT-A-treated sites had a significantly lower degree of hyperpigmentation than the control site in lightness index and hyperpigmentation scores from blinded physician and participants (p < .05). However, no statistically significant difference was observed between different concentrations of BoNT-A. No side effects were observed throughout the study period., Conclusion: Intradermal BoNT-A injection provided a protective effect from UVB-induced hyperpigmentation. It may be used for other hyperpigmentation disorders that are aggravated by UVB., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Isobutylamido thiazolyl resorcinol (ITR, Thiamidol ® ) has been proposed as a potent tyrosinase inhibitor. A formulation containing ITR has recently shown promising efficacy for the treatment of some hyperpigmentary conditions., Objectives: This study aimed to evaluate the efficacy and safety of ITR in the prevention of ultraviolet (UV)-induced hyperpigmentation in human skin., Materials and Methods: We performed a randomized, single-blinded, pilot study in 30 healthy participants. One arm was randomly assigned to receive an ITR-containing product for three weeks. Three hyperpigmented spots were induced by UVB irradiation on both arms after 3 weeks of ITR application. Outcome evaluations included measuring mean lightness index (*L) obtained by colorimeter, hyperpigmentation scores by visual analog scale (VAS), and adverse effects., Results: Both experimental sides showed no significant difference in terms of skin lightening after ITR application. However, the ITR-treated sides showed a statistically significant lower mean lightness index compared to control after an induction with UVB. In addition, the ITR-treated sides had an earlier improvement and resumed the normal skin color after 3 weeks post-UVB induction. A clinical evaluation by a blinded nontreating physician and subjects was more favorable on the ITR-treated side than the control side (P < .05). No significant side effect was noted., Conclusions: ITR is an effective agent in the prevention of pigmentary change from UVB irradiation and may serve as a promising agent for preventing other hyperpigmentary conditions., (© 2020 Wiley Periodicals LLC.)