Should anti-tuberculosis therapy be prescribed in erythema induratum? A case-controlled and incidence correlation study between 2001 to 2020 in Taiwan.

BACKGROUND: Erythema induratum (EI) is a tuberculid associated with Mycobacterium tuberculosis (TB) infection. TB has been identified in Taiwan with a high percentage of EI using PCR. However, this pathogen has rarely been detected recently. OBJECTIVE: To explore the association between EI, annual incidence of tuberculosis in Taiwan, and treatment outcomes over the past two decades. METHODS: Patients diagnosed with EI between 2001 and 2020 were enrolled based on histopathology, tissue culture, and TB-PCR tests. Other cases of panniculitis with TB-PCR results were used as controls. Their clinical information was obtained. The results were correlated with the annual incidence of tuberculosis and compared between groups. RESULTS: Fifty-five specimens from EI patients fulfilled the inclusion criteria; three (3/55, 5%) had positive TB PCR. One patient diagnosed with erythema nodosum in the control group had positive TB PCR (1/27, 4%). There was no significant relationship between TB and EI (odds ratio = 1.5, 95% confidence interval = -0.964 to 3.964, p = 1). Correlation between the incidence of TB and number of EI cases was not significant (r = -0.185, p = 0.447). Only four patients received anti-tuberculosis therapy. They all showed clinical improvement without recurrence. One patient with PCR-positive EI was not treated with anti-tuberculosis therapy; however, the skin lesion improved 3 months later. No other patients in the EI group were diagnosed with TB infection in the follow up of 508 person-years. CONCLUSIONS: Most EI in Taiwan are nodular vasculitis and not tuberculids owing to well-controlled tuberculosis. This condition can be alleviated without anti-tuberculosis therapy.

Training With Uncertain Annotations for Semantic Segmentation of Basal Cell Carcinoma From Full-Field OCT Images.

Semantic segmentation of basal cell carcinoma (BCC) from full-field optical coherence tomography (FF-OCT) images of human skin has received considerable attention in medical imaging. However, it is challenging for dermatopathologists to annotate the training data due to OCT's lack of color specificity. Very often, they are uncertain about the correctness of the annotations they made. In practice, annotations fraught with uncertainty profoundly impact the effectiveness of model training and hence the performance of BCC segmentation. To address this issue, we propose an approach to model training with uncertain annotations. The proposed approach includes a data selection strategy to mitigate the uncertainty of training data, a class expansion to consider sebaceous gland and hair follicle as additional classes to enhance the performance of BCC segmentation, and a self-supervised pre-training procedure to improve the initial weights of the segmentation model parameters. Furthermore, we develop three post-processing techniques to reduce the impact of speckle noise and image discontinuities on BCC segmentation. The mean Dice score of BCC of our model reaches 0.503±0.003, which, to the best of our knowledge, is the best performance to date for semantic segmentation of BCC from FF-OCT images.

A retrospective study on the direct immunofluorescence findings in pigmented purpuric dermatosis.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is characterized by grouped petechiae, purpuric macules, and pigmentation in the bilateral lower extremities. It runs a chronic and relapsing course. Pathophysiology is poorly understood, but it has been proposed to be an immune-complex disease or capillaritis. This study aimed to determine the incidence and patterns of positive direct immunofluorescence (DIF) findings in patients with clinically and histopathologically confirmed PPD. The association between DIF deposition type and clinical profile was also analyzed. METHODS: Patients with a clinical and histopathologic PPD diagnosis who had undergone DIF studies at a tertiary medical center with attached dermatopathology and immunofluorescence diagnostic centers between January 2002 and December 2021 were included in this study. Data on age, sex, disease duration, comorbidities, and drug intake were collected from medical records. RESULTS: There were 65 patients who satisfied the inclusion criteria. Among them, 58 (89%) had at least one positive finding and 53 (82%) were vascular deposition of immunoglobulin (Ig), complement, or fibrinogen. The most common vascular deposition was fibrinogen (71%) followed by C3 (62%), IgM (18%), IgA (6%), and IgG (3%). Fibrinogen deposition was associated with hypertension (p < 0.03). There was no association between vascular DIF deposition of IgG, IgA, and C3, with age, sex, comorbidities, disease duration, and drug history. CONCLUSION: The most common DIF findings in PPD were vascular deposition of fibrinogen and C3, with or without Ig presence. DIF findings supported a vascular origin in PPD but not an immune complex-mediated disease. Hypertension was associated with fibrinogen deposition and may play a role in its pathophysiology.

Generalized early inflammatory morphea mimicking interstitial T-cell lymphoma: A diagnostic pitfall.

Early generalized morphea can clinically mimic mycosis fungoides. The microscopic features of early inflammatory morphea may show variable degrees of infiltration and do not have the characteristic dermal collagen sclerosis. We report the case of a 63-year-old female patient who presented with a 2-month history of an asymptomatic skin rash. Physical examination revealed multiple erythematous to dusky patches on the trunk and thighs, resembling the patch stage of mycosis fungoides. Two skin biopsies were performed, both of which showed prominent interstitial lymphoid infiltration in the reticular dermis without dermal sclerosis. Small lymphocyte exocytosis and lining along the dermal-epidermal junction were observed focally in the epidermis. Small clusters of plasma cells and eosinophils were observed in perivascular areas. Although no predominant clonality was found for CD4 and CD8 stains, 50% loss of CD5 antigen and 90% loss of CD7 antigen expression were apparent in immunohistochemical studies. Subsequent blood tests showed a normal blood cell count and positive human T-lymphotropic virus Type 1 antibodies. The overall findings suggested interstitial mycosis fungoides or early adult T-cell lymphoma-leukemia. The patient refused aggressive treatment, and 3 months later, she presented with indurated plaques from the previous rash. A repeat biopsy revealed the typical features of morphea. This report discussed the pitfalls in the clinical and histopathological diagnosis of early generalized inflammatory morphea that both clinicians and pathologists should consider.

Adaptability of melanocytes post ultraviolet stimulation in patients with melasma.

BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.

A Case Series With Acquired Dermal Melanocytosis: A Retrospective Study From 2001 to 2018.

ABSTRACT: Acquired dermal melanocytosis (ADM) is a pigmented lesion caused by melanocytes in the dermis, and it is most often observed on the face of young and middle-aged Asian women. ADM development may be associated with melanin synthesis alterations, but little evidence of its molecular and histological alteration has yet been reported. This study aimed to evaluate ADM in different body locations using different immunohistochemical and chemical staining techniques. This retrospective case series includes consecutive patients confirmed as ADM by biopsy between 2001 and 2018. Patient data and archival images were used to determine the pattern and duration of skin lesions, as confirmed by data analysis of immunohistopathological staining of skin biopsy specimens. A total of 22 ADM patients were included with mean age at diagnosis of 47 years, and 63.6% were female. The most common site was limbs (36.4%), followed by face (27.3%), trunk (22.7%), and scalp (13.6%). Melanin levels were highest in the face and upper extremities and lowest in the trunk. All participants had perivascular distribution of dermal melanocytes, particularly on the face and limbs. The perineural distribution of dermal melanocytes was observed in the lower limbs, with prominent inflammation and fibrosis on the scalp. Dermal melanocytes expressed most markers recognizing melanocytes except for CD117. Analysis of this ADM case series has confirmed that melanin is activated by dermal melanocytes that may aggregate along blood vessels. CD117 may be a useful biomarker by which to identify the migration of epidermal melanocytes.

Blastomycosis-like pyoderma: A pitfall for the misdiagnosis of squamous cell carcinoma.

Blastomycosis-like pyoderma is a rare cutaneous disease presenting as solitary or multiple verrucous or ulcerated plaques and nodules in a susceptible patient. The diagnostic criteria include characteristic verrucous plaques with pustules and elevated borders, histopathologic findings of pseudoepitheliomatous hyperplasia with abscesses, growth of at least one bacterium in tissue culture, and exclusion of other infectious sources. This report describes a case of a 62-year-old man with poorly controlled type 2 diabetes mellitus who presented with plaques, nodules, and ulcers in both groins and the right ankle. The patient was initially misdiagnosed with multiple squamous cell carcinomas and underwent several operations. A review of the pathology slides revealed pseudoepitheliomatous hyperplasia with multiple dermal abscesses, while repeated wound and tissue cultures were positive for coagulase-negative Staphylococcus. Blastomycosis-like pyoderma was diagnosed. The patient was subsequently treated with culture-guided prolonged antibiotic therapy followed by intralesional steroid injection, which led to gradual resolution of the lesions.

Photoaging and Sequential Function Reversal with Cellular-Resolution Optical Coherence Tomography in a Nude Mice Model.

Although nude mice are an ideal photoaging research model, skin biopsies result in inflammation and are rarely performed at baseline. Meanwhile, studies on antiphotoaging antioxidants or rejuvenation techniques often neglect the spontaneous reversal capacity. Full-field optical coherence tomography (FFOCT) can acquire cellular details noninvasively. This study aimed to establish a photoaging and sequential function reversal nude mice model assisted by an in vivo cellular resolution FFOCT system. We investigated whether a picosecond alexandrite laser (PAL) with a diffractive lens array (DLA) accelerated the reversal. In the sequential noninvasive assessment using FFOCT, a spectrophotometer, and DermaLab Combo®, the photodamage percentage recovery plot demonstrated the spontaneous recovery capacity of the affected skin by UVB-induced transepidermal water loss and UVA-induced epidermis thickening. A PAL with DLA not only accelerated skin barrier regeneration with epidermal polarity, but also increased dermal neocollagenesis, whereas the nonlasered group still had >60% collagen intensity loss and 40% erythema from photodamage. Our study demonstrated that FFOCT images accurately resemble the living tissue. The photoaging and sequential function reversal model provides a reference to assess the spontaneous recovery capacity of nude mice from photodamage. This model can be utilized to evaluate the sequential noninvasive photodamage and reversal effects after other interventions.

Factors facilitating clinical application of and adherence to evidence-based healthcare among medical professionals attending national competitions in Taiwan: a study based on the decomposed theory of planned behaviour.

BACKGROUND: Implementing evidence-based healthcare (EBHC) to improve the quality of patient care is a key issue for physicians and nurses. One of the most effective activities for achieving this is the annual topic-oriented clinical application national competition in Taiwan. Hundreds of clinical issues have been presented in this competition. By using the decomposed theory of planned behaviour (DTPB), this study explored physicians' and nurses' behaviour and adherence to the clinical application of EBHC after participating in the competitions. METHODS: We conducted a 3-month cross-sectional online survey using a structured questionnaire adapted from the original study of the DTPB to collect behavioural and intention-related data. We also used a model of seven action stages (from aware of to adhered to) to assess target behaviours. We targeted contestants of the EBHC competitions between 1999 and 2017 as study participants. Of 631 teams, 321 teams completed the questionnaire, representing a 49.5% response rate. We applied structural equation modelling to test model fit. Moreover, we executed multivariate logistic regression to identify potential predictors. RESULTS: Of the respondents, 33.3% reportedly reached the final adhered to stage. The DTPB model exhibited a good fit to the observed data. All constructs (usefulness, compatibility, peer influence, superior influence, self-efficacy, resource facilitating conditions, attitude, subjective norms, behavioural control, and intentions) were positively associated with the target behaviours, except for ease of use and technology facilitating conditions. Furthermore, the study model explained the variance in the target behaviours (37.0%). Having managerial duties (odds ratio [OR] =2.03, 95% confidence interval [CI] =1.10-3.77), resource facilitating conditions (OR = 1.06, 95% CI = 1.01-1.11), behavioural control (OR = 2.21, 95% CI = 1.47-3.32), and intentions (OR = 1.96, 95% CI = 1.40-2.73) were significant predictors of the achievement of the adhered to stage. CONCLUSIONS: The study demonstrated the association between determinants of behaviour and clinical applications and factors influencing adherence to EBHC among competition participants. The adherence rate was not high after the competitions, and this may be improved by promoting certain factors associated with the target behaviours.

Spongiotic Pattern in Pemphigus: A Retrospective Observational Single-Center Study.

Pemphigus is a chronic blistering disorder caused by autoantibodies that target desmosomal proteins in the epidermis. Acantholysis may be absent, and pemphigus may present only with spongiosis and vesiculation, thereby leading to a misdiagnosis of eczema. Herein, we conducted a retrospective, observational, single-center study to establish a pattern of spongiosis in cases of pemphigus confirmed by direct immunofluorescence. Immunopathologically diagnosed pemphigus specimens from 2001 to 2020 were retrieved, and specimens with spongiosis were analyzed for the following features: vesiculation, acantholysis, spongiosis, inflammatory cells in the epidermis, and inflammation in the dermis. Cases of spongiotic dermatitis were used as control. Out of 99 immunopathologically diagnosed pemphigus specimens, 41 samples with spongiosis were identified. About one quarter of the specimens did not have acantholysis. Spongiosis in the middle to lower thirds of the perilesional epidermis (p = 0.030), exocytosis with either neutrophils or eosinophils (p = 0.016), dermal infiltrates composed of lymphocytes, eosinophils, and neutrophils (p = 0.012), and absence of Langerhans cell microabscesses (p < 0.001) were more common in pemphigus than control. Spongiosis in pemphigus may mimic eczema in patients without acantholysis. The subtle histological findings in this study provide diagnostic clues and suggest that further immunofluorescence should be performed to confirm pemphigus diagnosis.

Application of Cellular Resolution Full-Field Optical Coherence Tomography in vivo for the Diagnosis of Skin Tumours and Inflammatory Skin Diseases: A Pilot Study.

BACKGROUND: Optical coherence tomography (OCT) has been shown to provide non-invasive diagnosis of common skin neoplasms, especially basal cell carcinoma. OCT produces a cross-sectional view of the tissue, similar to a traditionally sectioned histopathological view, but the resolution of conventional OCT is low and thus limits clinical application. OBJECTIVES: This study aimed to investigate the application ability of a full-field (FF)OCT system which was newly developed to scan the skin at the cellular level. METHODS: Patients with skin tumours or inflammatory lesions warranting biopsy were consecutively enrolled. All lesions underwent clinical, dermoscopic, and OCT assessment, followed by routine biopsy. The adjacent normal skin was scanned for comparison. OCT images were interpreted (blinded to the biopsy results) and then compared with the histopathological diagnosis. RESULTS: A total of 111 patients with 115 lesions completed the protocol, including 80 skin tumours, 28 inflammatory diseases, and 7 other diseases. Of the OCT images, 43.5% were of good quality and show expected features. Identifiable features of actinic keratosis, Bowen's disease, basal cell carcinoma, extramammary Paget's disease, seborrheic keratosis, large cell acanthoma, bullous pemphigoid, interface dermatitis, lichenoid tissue reaction, and psoriasis were demonstrated. Lesions are located deeply, and so some features were out of the field of view, accounting for 40.0% (46/115). CONCLUSIONS: This study expanded the ability of FFOCT for the clinical diagnosis of various skin conditions. This new optical technique can clearly visualise skin lesions located in the epidermis and upper dermis. It provided an effective way to perform digital skin biopsy in superficial skin diseases.

Pathological and Immunohistochemical Characteristics of Granuloma and Lymphatics in Cheilitis Granulomatosa.

ABSTRACT: Cheilitis granulomatosa (CG) is an idiopathic, rare, and chronic granulomatous disorder involving the lips. We characterized the pathological and immunohistopathological findings of these granulomas and their relationship with the lymphatic vessels. Pathologically confirmed cases of primary CG from 2001 to 2016 were collected. Cases of inflammatory cheilitis without the presence of granuloma were included in the control group. Demographic data, clinical presentation, response to therapy, and pathological differences were compared. Periodic acid-Schiff and acid-fast stains excluded patients having infections. CD68, CD163, and D2-40 stains demonstrated features of granuloma, macrophage polarization, and the relationship between granuloma and lymphatic vessels. Thirteen patients diagnosed with CG were enrolled. Thirteen people were enrolled in the control group. The granulomas were either mononuclear or sarcoidal. They were predominantly positive for CD68 but negative for CD163. Perilymphatic granulomas were found in all patients. Intralymphatic histiocytosis and lymphatic dilatation were more commonly observed in patients diagnosed with CG than those in controls (54% vs. 15%, P = 0.03 and 92% vs. 23%, P < 0.01). TH1 immune response due to CD68+ M1 macrophages results in CG. Perilymphatic aggregation of macrophages and intralymphatic histiocytosis were important pathological clues for diagnosis.

Computer-Aided Detection (CADe) System with Optical Coherent Tomography for Melanin Morphology Quantification in Melasma Patients.

Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and bias. We used a cellular resolution full-field optical coherence tomography (FF-OCT) to assess melanin features of melasma lesions and perilesional skin on the cheeks of eight Asian patients. A computer-aided detection (CADe) system is proposed to mark and quantify melanin. This system combines spatial compounding-based denoising convolutional neural networks (SC-DnCNN), and through image processing techniques, various types of melanin features, including area, distribution, intensity, and shape, can be extracted. Through evaluations of the image differences between the lesion and perilesional skin, a distribution-based feature of confetti melanin without layering, two distribution-based features of confetti melanin in stratum spinosum, and a distribution-based feature of grain melanin at the dermal-epidermal junction, statistically significant findings were achieved (p-values = 0.0402, 0.0032, 0.0312, and 0.0426, respectively). FF-OCT enables the real-time observation of melanin features, and the CADe system with SC-DnCNN was a precise and objective tool with which to interpret the area, distribution, intensity, and shape of melanin on FF-OCT images.

Plaque-Type Variant of Acquired Rhabdomyomatous Mesenchymal Hamartoma on the Chin: A Case Series.

ABSTRACT: Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare benign tumor composed of skeletal muscle fibers and other mesenchymal-derived cells. The lesions are generally solitary sessile papules or skin tag lesions that occur during childhood. We retrospectively reviewed patients diagnosed with RMH pathologically between January 2001 and June 2020 at a tertiary medical center. A literature review was conducted. Seven plaque-type RMHs on the chin were found, including 6 in adults and one in a 14-year-old boy. The average age was 45.7 years. The onset of the RMH appearance was between several months and years. Pathologically, all patients showed a scattered haphazard arrangement of skeletal muscle bundles in the dermis and/or subcutis. Subcutis replaced by fibrous tissue and skeletal muscle bundles was present in 2 cases. Some skeletal muscles had a periadnexal distribution. This case series demonstrated a distinct clinical presentation of acquired RMH specifically located on the chin.

Isotopic response of labetalol-associated lichen planus pemphigoides on an old radiation site: A case report.

Over the years, the occurrences of different types of skin disorders arising from radiation sites have been observed and studied. Examples include autoimmune blistering diseases such as pemphigus, pemphigoid, and interface or inflammatory reaction patterns such as lichen planus, lupus erythematosus, and Stevens-Johnson syndrome. The phenomenon whereby a new skin disorder arises from a previously healed or irradiated site is called an isotopic response, described as a type of Koebner phenomenon. Ionizing radiation itself can profoundly affect the skin. Both early and late changes can present, which typify the progression of changes following irradiation of the skin. Herein, we report a rare case of labetalol-associated lichen planus pemphigoides that occurred at the site treated with radiation for a soft tissue malignancy after 19 years as a result of an isotopic response. The rash was well-controlled after therapy and kept a 4-year remission. The same skin reaction recurred after the reintroduction of labetalol 4 years later.

Cutaneous Pseudolymphoma With Langerhans Cell Hyperplasia-A Rare Case With Clinical Presentation Mimicking Malignancy and Potential Diagnostic Pitfall.

ABSTRACT: We describe a rare case of cutaneous pseudolymphoma with Langerhans cell hyperplasia. An 84-year-old female patient presented with erythematous and pernicious-looking plaques on her scalp that had been present for months. Histologically, lymphoid follicles consisting of mixed-type lymphocytes and Langerhans cells were aggregated focally. The diagnosis was verified by several immunohistochemical stains and by clinical evaluation. Skin lesions were steadily resolved with low-dose corticosteroid and hydroxychloroquine.

In vivo dual-mode full-field optical coherence tomography for differentiation of types of melanocytic nevi.

SIGNIFICANCE: Melanocytic nevi represent the most common dermal melanocytic lesions in humans. Nevus is typically diagnosed clinically with the naked eye or with dermoscopy. However, it is essential to identify the type of nevus by invasive biopsy for histopathological examination. The use of noninvasive imaging tools can be used to evaluate the types of nevi to reduce unnecessary excisions of benign entities. AIM: To evaluate the feasibility of using en face and cross-sectional full-field optical coherence tomography (FF-OCT) in differentiation of melanocytic nevi that can facilitate the reduction of unnecessary excisions of benign entities. APPROACH: Dual-mode Mirau-type FF-OCT for cross-sectional imaging (B-scan) and en face imaging were used to distinguish the types of nevi. RESULTS: Although the B-scan reveals the distribution of melanosomes, users can set a specific depth of the en face image to explore the morphology of surrounding skin cells instantly. According to the locations of nevus nests, the different types of nevi, including junction nevus and compound nevus, can be identified using this dual-mode FF-OCT system. CONCLUSIONS: Combining B-scan and en face imaging in vivo FF-OCT enables the examination and navigation of skin tissues in real time and in three dimensions.