Recent treatment and prognosis in 643 patients with extramammary Paget's disease.

Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.

Immunohistochemical dissection of cystic panfolliculoma focusing on the expression of multiple hair follicle lineage markers with an insight into the pathogenesis.

Panfolliculoma (PF) is a rare benign tumor with signs of differentiation toward all components of the hair follicle (HF). Cystic panfolliculoma (CPF) is a subset of PF with histological similarity to trichofolliculoma making the differential diagnosis difficult in some cases. Immunohistopathological investigations of PF have been reported; however, previous studies focused mostly on the expression profile of the outer root sheath markers. Herein, we report a case of CPF. A panel of antibodies was developed and used for the detection of the expression of cytokeratin (CK) 10, CK13, CK14, CK15, hair-hard keratin (AE13) and EpCAM within the lesion, supporting the differentiation of all epithelial lineages of the HF and the diagnosis of CPF. Immunohistopathological examinations clearly showed the spatial distribution pattern of each subset of tumor cells with distinct HF differentiation marker expression. Intriguingly, fibroblastic dermal cells were distributed preferentially near CK15-negative epithelium or CK13-positive HF-like structures, suggesting a role for epithelial-mesenchymal interactions (EMIs) in CPF pathogenesis. Further characterization of EMIs between the tumor and surrounding mesenchymal cells in CPF may provide an explanation for immature HF differentiation. These findings suggest that the more intense and coordinated EMI in the analogous tumorigenesis gives rise to mature HF structures, resulting in trichofolliculoma, which may explain their histological resemblance.

Multiple subcutaneous abscesses by Corynebacterium amycolatum in a patient with severe idiopathic aplastic anaemia.

Corynebacterium amycolatum is a part of the normal skin flora and has been underestimated as a pathogen. However, in recent years, the species has gained recognition as an important pathogen causing severe infections, particularly in immunocompromised patients. Nevertheless, identifying these organisms at the species level is difficult in routine clinical microbiology, leading to limited knowledge of their clinical manifestations in infectious diseases. In this study, we report a rare case of multiple subcutaneous abscesses in a patient with severe neutropenia, wherein C.amycolatum was identified as the causative organism through genotyping tests. This case highlights the importance of this organism as an aetiological agent of severe skin infections in patients with compromised immune systems.

Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases.

Hair-loss diseases comprise heterogenous conditions with respective pathophysiology and clinicopathological characteristics. Major breakthroughs in hair follicle biology and immunology have led to the elucidation of etiopathogenesis of non-scarring alopecia (e.g., alopecia areata, AA) and cicatricial alopecia (e.g., lichen planopilaris, LPP). High-throughput genetic analyses revealed molecular mechanism underlying the disease susceptibility of hair loss conditions, such as androgenetic alopecia (AGA) and female pattern hair loss (FPHL). Hair loss attracted public interest during the COVID-19 pandemic. The knowledge of hair loss diseases is robustly expanding and thus requires timely updates. In this review, the diagnostic and measurement methodologies applied to hair loss diseases are updated. Of note, novel criteria and classification/scoring systems published in the last decade are reviewed, highlighting their advantages over conventional ones. Emerging diagnostic techniques are itemized with clinical pearls enabling efficient utilization. Recent advances in understanding the etiopathogenesis and management for representative hair diseases, namely AGA, FPHL, AA, and major primary cicatricial alopecia, including LPP, are comprehensively summarized, focusing on causative factors, genetic predisposition, new disease entity, and novel therapeutic options. Lastly, the association between COVID-19 and hair loss is discussed to delineate telogen effluvium as the predominating pathomechanism accounting for this sequela.

Prevalence of alopecia areata in Japan: Estimates from a nationally representative sample.

Data on the prevalence of alopecia areata (AA) in Japan is limited and the epidemiology of the disease there is not well understood; therefore, it is critical to examine the prevalence and severity of AA in Japan to inform the need for future treatments and research. A cross-sectional, web-based survey was conducted in Japan from January through March 2021. A total of 45 006 participants were identified through general population survey panels and asked about their experience with AA and hair loss. The Alopecia Assessment Tool and the Scalp Hair Assessment PROTM were adopted to screen for history of AA and assess disease severity, respectively. Eligible participants submitted photos of their scalp, which were reviewed by three board-certified dermatologists to evaluate the presence and severity of AA. Prevalence and severity estimates were calculated using participants' self-reported data and verified through the dermatologists' assessments. The participant-reported point prevalence of AA was 2.18%. The adjusted point prevalence following physician adjudication using participant-submitted photos was 1.45%. Topical corticosteroids were the most commonly used treatments, with 34.6% of participants diagnosed with AA reported having ever used them. Participants also reported negative impacts on their mood (70.2%), self-esteem (55.8%), and social interactions (48.9%). Despite the social and emotional impact of hair loss, more than one third of those reporting a physician diagnosis of AA were not currently seeking treatment. The current study identified an estimated prevalence of AA in Japan between 1.45% and 2.18% based on the survey results and physician-adjudication of those findings. Considering the impactful psychological burden of AA, the survey results showing that 38.90% of surveyed patients do not currently seek treatment may indicate an unmet need for remedies.

Invention of automated numerical algorithm adopting binarization for the evaluation of scalp hair coverage: An image analysis providing a substitute for phototrichogram and global photography assessment for hair diseases.

BACKGROUND: The efficacy of therapeutic modalities for hair disease can be evaluated globally by photo assessment and more precisely by phototrichogram (PTG). However, the latter procedure is laborious, time consuming, subject to inter-observer variation, and requires hair clipping. OBJECTIVE: To establish an automated and patient/investigator friendly methodology enabling quantitative hair amount evaluation for daily clinical practice. METHODS: A novel automated numerical algorithm (aNA) adopting digital image binarization (i.e., black and white color conversion) was invented to evaluate hair coverage and measure PTG parameters in scalp images. Step-by-step improvement of aNA was attempted through comparative analyses of the data obtained respectively by the novel approach and conventional PTG/global photography assessment (GPA). RESULTS: For measuring scalp hair coverage, the initial version of aNA generally agreed with the cumulative hair diameter as assessed using PTG, showing a coefficient of 0.60. However, these outcomes were influenced by the angle of hair near the parting line. By integrating an angle compensation formula, the standard deviation of aNA data decreased from 5.7% to 1.2%. Consequently, the coefficient of determination for hair coverage calculated using the modified aNA and cumulative hair diameter assessed by PTG increased to 0.90. Furthermore, the change in hair coverage as determined by the modified aNA protocol correlated well with changes in the GPA score of images obtained using clinical trials. CONCLUSION: The novel aNA method provides a valuable tool for enabling simple and accurate evaluation of hair growth and volume for clinical trials and for treatment of hair disease.

Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 µm/cm2 , 13069.1 ± 10960.7 µm2 /cm2 , and 0.9 ± 0.9 µm (ratios vs. baseline: +1.4%, +3.4%, and +2.2%), respectively. The female and high terminal hair ratio groups achieved better improvement. Of the total participants, 62.9% noted some degree of improvement. No serious adverse events were detected. This novel approach exhibited visible effects while ensuring safety and patient satisfaction. Therefore, it holds promise as a possible therapeutic option for treating PHL, especially in women.

Distinctive age distribution and hair loss pattern putatively highlighting uniqueness of Japanese cases of fibrosing alopecia in a pattern distribution.

Fibrosing alopecia in a pattern distribution (FAPD) is a unique entity which presents clinicopathological characteristics of both male/female pattern androgenetic alopecia (AGA) and lichen planopilaris (LPP). This entity was first reported in 2000 and its criteria was recently proposed. Etiopathogenesis of FAPD has been speculated to be immunological destruction involving miniaturized hair follicles but still remains elusive. To date, few Asian FAPD cases have been reported in the literature. In this study, Japanese FAPD cases were identified based on the aforementioned criteria and analyzed to delineate clinicopathological characteristics. By retrospectively revisiting medical records and clinical photographs, 24 Japanese cases comprising 17 women and seven men were diagnosed as FAPD. All male patients had disease onset by their early 30s, whereas most female patients had developed the condition in middle age or later. Their initial diagnoses prior to the diagnostic confirmation of FAPD were mostly LPP. Based on the clinical phenotypes, the cases were categorized into AGA and LPP types. These subtypes were characterized by foremost trichoscopic and histopathological findings of AGA or LPP, respectively. Unlike previously reported cases, our patients tended to manifest hair loss in both vertex and frontal to mid-scalp with minimal regression of anterior hairline, manifesting unique "parachute" pattern, which has been reported as a representative characteristic of East Asian AGA in the literature. Anti-inflammatory therapies seemed to be effective to deter hair loss but insufficient to achieve improvement. Further accumulation of the cases is necessary; however, these findings may provide additional pathophysiological insights into FAPD and highlight uniqueness of the etiology and clinical phenotype of Japanese FAPD putatively influenced by racial predispositions.

Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines.

Alopecia areata (AA) is a relatively common nonscarring hairloss disease characterized by an autoimmune response to anagen hair follicles (HFs). Accumulated evidence suggests that collapse of the HF immune privilege subsequent to triggering events, represented by viral infection, leads to autoimmune response in which autoreactive cytotoxic CD8+NKG2D+ T cells mainly target exposed HF autoantigens. AA had been recognized as type 1 inflammatory disease, but recent investigations have suggested some roles of type 2- and Th17-associated mediators in AA pathogenesis. The significance of psychological stress in AA pathogenesis is less emphasized nowadays, but psychological comorbidities, such as depression and anxiety, attract greater interest in AA management. In this regard, the disease severity may not solely be evaluated by the extent of hair loss. Use of trichoscopy markedly improved the resolution of the diagnosis and evaluation of the phase of AA, which is indispensable for the optimization of treatment. For the standardization of AA management, the establishment of guidelines/expert consensus is pivotal. Indeed, the Japanese Dermatological Association (JDA) and other societies and expert groups have published guidelines/expert consensus reports, which mostly recommend intralesional/topical corticosteroid administration and contact immunotherapy as first-line treatments, depending on the age, disease severity, and activity of AA. The uniqueness of the JDA guidelines can be found in their descriptions of intravenous corticosteroid pulse therapy, antihistamines, and other miscellaneous domestically conducted treatments. Considering the relatively high incidence of spontaneous regression in mild AA and its intractability in severe subsets, the importance of course observation is also noted. Evidenced-based medicine for AA is currently limited, however, novel therapeutic approaches, represented by JAK inhibitors, are on their way for clinical application. In this review, the latest understanding of the etiopathogenesis and pathophysiology, and update on therapeutic approaches with future perspectives are summarized for AA, following the current version of the JDA AA management guidelines.

Clinicopathological insight into self-reported hair loss with no findings: How do we manage this enigmatic condition?

Patients who complain of hair loss without any supportive findings can be encountered in daily practice. To provide insight into this embarrassing condition, we retrospectively reviewed medical charts of eight cases with self-reported hair loss with no findings (SHLNOF). High frequency in middle aged women and concomitance of thyroid and gynecological problems were revealed. Four patients reported scalp dysesthesia/trichodynia. Two patients underwent scalp biopsy, both of which demonstrated increase in indeterminate hairs, suggesting mild hair miniaturization. Supportive medical consultation coupled with the presentation of clinical and trichoscopic images reassured the majority of the patients. These findings suggested that SHLNOF should not be disregarded simply as a misconception. A non-biased and diligent workup should be conducted to better manage this enigmatic condition.

Long-term remission of unusual plasmoacanthoma on the nasal canthus achieved by intralesional corticosteroid injection: Insights into the pathogenesis and treatment planning based on a literature review.

Plasmoacanthoma (PA) is a verrucous tumor predominantly developing on periorificial areas, which has been considered as an unusual subtype of plasmacytosis circumorificialis. Because of its rarity and clinical resemblance to several verrucous dermatological disorders, accurate diagnosis of PA is quite challenging. Herein, we present an extremely unusual case of PA which arose on both sides of the nasal canthus and was successfully treated with intralesional corticosteroid injections. To elucidate clinicopathological features of this condition, a literature review was also attempted. A 78-year-old woman visited us with a 2-year history of eruptions affecting both sides of the nasal canthus. At a local clinic, the diagnosis and treatment had been unsuccessful due to non-specific histological findings, leading to the referral to our institute. On physical examination, verrucous and lobulated reddish plaques were observed. In histology, psoriasiform epidermal change and dense plasma cell infiltration in the dermis were detected. The diagnosis of PA was made. After 5-monthly intralesional triamcinolone acetonide injections, the lesions became hardly noticeable with no evidence of recurrence. A literature review found five PA cases. PA predominantly arose on the periorificial area, mostly in or around the mouth, except one case which developed on the extra-oral or perioral area. Intralesional corticosteroid injection has been preferably performed, which frequently achieved successful remission. Chronic inflammation has been reported as a preceding condition. Abundance of plasma cells in the lacrimal glands and conjunctiva, together with pre-existing allergic conjunctivitis and habitual scratching, might have contributed to PA development in our case. Histopathological detection of psoriasiform epidermal change and dense dermal plasma cell infiltration is indispensable for the diagnosis of PA. For accurate diagnosis, optimization of treatment, and further accumulation of extra-oral/perioral PA cases, a skin biopsy needs to be proactively performed on verrucous lesions on relatively unfamiliar orifice sites.

Development of a scoring system to predict outcomes of i.v. corticosteroid pulse therapy in rapidly progressive alopecia areata adopting digital image analysis of hair recovery.

Alopecia areata (AA) is a common autoimmune disease manifesting varying degrees of hair loss. Rapidly progressive AA (RP-AA) is a severe subtype of AA and often resistant to skin-directed treatments. i.v. corticosteroid pulse therapy has been applied for RP-AA; however, the treatment outcome can only become evaluable several months after the intervention, discomposing the patients. In this study, we attempted to develop a scoring system to predict treatment outcomes based on statistical correlations between newly identified predictors and the recovery rates calculated by digital image analysis. Thirty RP-AA patients (15 men and 15 women) who underwent pulse therapy and demonstrated total hair loss during the clinical course were included. The percentages of hair regrowth (%HR) at 6 months after the treatment were quantitatively calculated by image analysis software. The correlation between %HR and clinicopathological and immunological variables were statistically assessed. The analysis identified four confirmatory contributors including female sex (P = 0.015), absence of previous AA history (P = 0.02), lower peripheral blood eosinophil count (P = 0.02) and mild to moderate cell infiltration around the hair bulb (P = 0.034), together with a potential contributor, namely absence of atopic dermatitis in their medical history (P = 0.08). The scoring system was developed by double counting confirmatory variables and single counting a potential variable. Importantly, the scores obtained by this system demonstrated significant correlation with %HR (r = 0.61, P < 0.001). The usefulness of this scoring system was further validated by assessing additional 20 cases of RP-AA. When combined with a recently published algorithm for early detection of self-healing subset, the current scoring system may help strategize the therapeutic approach for RP-AA.

Human iPS Cell-Derived Cell Aggregates Exhibited Dermal Papilla Cell Properties in in vitro Three-Dimensional Assemblage Mimicking Hair Follicle Structures.

Current approaches for human hair follicle (HF) regeneration mostly adopt cell-autonomous tissue reassembly in a permissive murine intracorporeal environment. This, together with the limitation in human-derived trichogenic starting materials, potentially hinders the bioengineering of human HF structures, especially for the drug discovery and treatment of hair loss disorders. In this study, we attempted to reproduce the anatomical relationship between an epithelial main body and the dermal papilla (DP) within HF in vitro by three-dimensionally assembling columnarly molded human keratinocytes (KCs) and the aggregates of DP cells and evaluated how HF characteristics were reproduced in the constructs. The replaceability of human-induced pluripotent stem cell (hiPSC)-derived DP substitutes was assessed using the aforementioned reconstruction assay. Human DP cell aggregates were embedded into Matrigel as a cluster. Subsequently, highly condensed human KCs were cylindrically injected onto DP spheroids. After 2-week culture, the structures visually mimicking HFs were obtained. KC-DP constructs partially reproduced HF microanatomy and demonstrated differential keratin (KRT) expression pattern in HFs: KRT14 in the outermost part and KRT13, KRT17, and KRT40, respectively, in the inner portion of the main body. KC-DP constructs tended to upregulate HF-related genes, KRT25, KRT33A, KRT82, WNT5A, and LEF1. Next, DP substitutes were prepared by exposing hiPSC-derived mesenchymal cells to retinoic acid and subsequently to WNT, BMP, and FGF signal activators, followed by cell aggregation. The resultant hiPSC-derived DP substitutes (iDPs) were combined with KCs in the invented assay. KC-iDP constructs morphologically resemble KC-DP constructs and analogously mimicked KRT expression pattern in HF. iDP in the constructs expressed DP-related markers, such as vimentin and versican. Intriguingly, KC-iDP constructs more intensely expressed KRT33A, KRT82, and LEF1, which were stepwisely upregulated by the addition of WNT ligand and the mixture of WNT, SHH, and EDA signaling activators, supporting the idea that iDP exhibited biological properties analogous to DP cell aggregates in the constructs in vitro. These preliminary findings suggested the possibility of regenerating DP equivalents with in vitro hair-inductive capacity using hiPSC-derived cell composites, which potentially reduce the necessity of human tissue-derived trichogenic cell subset and eventually allow xeno-free bioengineering of human HFs.

Elucidation of demographic, clinical and trichoscopic features for early diagnosis of self-healing acute diffuse and total alopecia.

The term "acute diffuse and total alopecia" (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as "self-healing ADTA" (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 ± 15.9 years. The progression of hair loss areas peaked at 3.6 ± 1.5 months, and complete hair regrowth was achieved in 7.9 ± 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.

Two cases in which tofacitinib effectively treated both ulcerative colitis and alopecia areata.

A 40-year-old woman (case 1) visited the hospital complaining of diarrhea and was diagnosed with ulcerative colitis (UC). She was administered 5-aminosalicylic acid (5-ASA), but developed intolerance. Prednisolone (PSL) was administered, and her symptoms improved. However, alopecia areata developed as the PSL was tapered, and her UC relapsed. Adalimumab, Infliximab (IFX), and golimumab were used, but all showed insufficient efficacy. Therefore, we started tofacitinib (TOF). Her bloody stools and diarrhea improved 3 days after TOF administration, and clinical remission occurred on day 14. Her alopecia areata improved 14 days after starting TOF and improved completely during TOF maintenance therapy. A 19-year-old man (case 2) had developed alopecia areata at 10 years old and was diagnosed with UC at 17 years old. He achieved sustained remission with IFX, but then stopped IFX to receive a live vaccination. His UC relapsed 4 months later, immediately after the live vaccine was administered. Vedolizumab was administered, but was ineffective, as was re-administration of IFX. TOF was administered, and his clinical symptoms improved 7 days later. He achieved clinical remission on day 20. In addition, his hair began to regrow 14 days after starting TOF.

Use of trichoscopy for the diagnosis of alopecia areata coexisting with primary scarring alopecia in a female hair loss patient.

Despite patchy hair loss being typically observed in alopecia areata (AA), similar lesions can be seen in other forms of alopecia and the diagnosis is sometimes challenging. Of note, patchy primary scarring alopecia (SA) needs to be clearly distinguished from AA as SA can leave permanent hair loss. Herein, we report a previously unreported case of AA coexisting with SA successfully diagnosed by detailed trichoscopic investigation. A 42-year-old woman visited us with patchy hair loss lesions on the scalp. On physical examination, alopecic lesions sized up to 2 cm in diameter were observed in the right temporal and parietal regions. A gentle hair pull test collected dystrophic anagen hairs from some patches. Trichoscopy detected tapering hairs and black dots. The diagnosis of AA was made. However, some reddish patches were totally hair pull test negative, urging us to further evaluate the remaining lesions. Additional trichoscopic investigation revealed the disappearance of follicular ostia and the presence of a white and milky-red area and peripilar scales, suggestive of SA. In histology, the clinically AA lesion showed peribulbar cell infiltration, while the potentially SA lesion demonstrated inflammatory cell infiltration around the isthmus and the decrease in hair follicles, some of which were replaced by fibrotic tissue. The final diagnosis of AA coexisting with SA was made. Intralesional corticosteroid injection improved AA but not SA. These findings emphasize the need for thorough trichoscopic examination for accurate diagnoses of rare hair loss conditions.

Chronological clinicopathological characterization of rapidly progressive alopecia areata resistant to multiple i.v. corticosteroid pulse therapies: An implication for improving the efficacy.

Intravenous corticosteroid pulse therapy (pulse therapy) has been reported to be effective for rapidly progressive alopecia areata (RP-AA). Mostly, a single 3-day administration of corticosteroid (methylprednisolone 500 mg/day) has been performed in Japan; however, to what extent additional administrations improve the outcome has not been fully elucidated. To assess the advantage of repeating the pulse therapy to RP-AA cases refractory to the initial intervention, retrospective clinicopathological analysis was performed. Detailed chronological analysis was conducted in eight cases (one man and seven women; average age, 38.3 ± 10.4 years) demonstrating total scalp hair loss 3 months after the first pulse therapy and treated with additional rounds of the pulse therapy. All cases manifested total hair loss, scalp edema, itch or pain on the scalp after the initial intervention. Histopathological analyses of affected lesions prior to additional pulse therapies revealed persisting dense perifollicular lymphocytic inflammation in all cases. Interestingly, such inflammatory change tended to be severer when compared with previously reported pulse therapy good responders. Extra pulse therapy resulted in partial regrowth of terminal hairs in three out of eight cases, but all of them experienced relapse in the long run. The literature review also suggested limited efficacy of repeating pulse therapy to severe AA cases. These findings suggested that the efficacy of currently conducted repetitive pulse therapy is limited in RP-AA cases with extensive perifollicular inflammation and resistant to the initial pulse therapy. Modulation of the dose and the interval of intervention, in combination with alternative approaches, may be required to achieve a successful outcome.

Cutaneous Metaplastic Synovial Cyst: Case Report and Literature Review from the Dermatological Point of View.

Cutaneous metaplastic synovial cysts (CMSCs) are rare tumors typically comprising a solitary, well-circumscribed cystic mass that is not connected to the joint. Synovial cysts have been reported predominantly by orthopedists or pathologists; however, the presence of CMSC is not generally well recognized by dermatologists. Herein, we report a CMSC in a 68-year-old woman receiving systemic corticosteroid therapy for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). We attempt to delineate the clinical characteristics of this unusual neoplasm by reviewing the literature, focusing especially on dermatological descriptions. Histologic examination of the surgical specimen in the current case revealed that the cystic wall was lined with layers of flattened synovial cell-like cells and connective tissues, mimicking the synovial membrane. Positive immunoreactivity of the lining cells against vimentin was detected, but no immunoreactivity against cytokeratin, carcinoembryonic antigen (CEA), CD68, or S-100 was detected. The pathogenesis of CMSC remains unclear, but it has been tightly linked to direct traumatic stimuli or relative tissue fragility, which potentially accounts for CMSC development in our case. Most CMSCs reported by dermatologists are located on the extremities, whereas those described by other specialists tend to be distributed more globally. Preoperative diagnoses are often either epidermal cyst or suture/foreign body granuloma. Incomplete surgical excision of usual synovial cysts may lead to local recurrence, which has been reported in oral and maxillofacial surgery, but not in dermatologic surgery. This fact could be explained by the technical difficulties of surgical excision related to anatomical location. Dermatologists need to be aware of CMSC, and CMSC should be included in the differential diagnosis of subcutaneous cysts.