Correlations between histopathologic findings, serum biomarker levels, and clinical outcomes in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.

Case Report: Simple Nodular Cutaneous Leishmaniasis Caused by Autochthonous Leishmania (Mundinia) orientalis in an 18-Month-Old Girl: The First Pediatric Case in Thailand and Literature Review.

We report an autochthonous case of simple, localized cutaneous leishmaniasis in a healthy 18-month-old girl from southern Thailand. The patient presented with a solitary chronic cutaneous nodular lesion on her left cheek for approximately 1 year. Histopathological dissection of the cheek skin biopsy demonstrated remarkably nodular and interstitial infiltrates of lymphocytes and histiocytes full of intracellular oval-shaped amastigotes, consistent with cutaneous leishmaniasis. The Leishmania promastigotes were also cultured successfully from the lesion biopsy and were designated with the WHO code MHOM/TH/2021/CULE5. Using internal transcribed spacer 1-specific polymerase chain reaction, the parasite DNA was demonstrated in both saliva and lesion biopsy. Based on the BLASTn and phylogenetic analysis, the parasite was identified as Leishmania orientalis, clustered in the Mundinia subgenus. The patient responded well to a 6-week course of oral itraconazole, without recurrence. To our knowledge, this is the fourth case of autochthonous leishmaniasis resulting from L. orientalis and the youngest patient of leishmaniasis ever reported in Thailand. More importantly, we also demonstrate the clinical course of the lesion according to the timeline before and after treatment, which can help physicians better understand and provide an accurate diagnosis with appropriate treatment of this emerging parasitic disease.

B1 repetitive sequence methylation enhances wound healing of second-degree burns in rats.

The accumulation of DNA damage in burn wounds delays wound healing. DNA methylation by short interspersed nuclear element (SINE) small interfering (si)RNA prevents DNA damage and promotes cell proliferation. Therefore, SINE siRNA may be able to promote burn wound healing. Here, a SINE B1 siRNA was used to treat burn wounds in rats. Second-degree burn wounds were introduced on the backs of rats. The rats were then divided into three groups: a B1 siRNA-treated, saline-treated control, and saline + calcium phosphate-nanoparticle-treated control group (n=15/group). The wounds were imaged on days 0, 7, 14, 21 and 28 post-injury. The tissue sections were processed for methylation, histological and immunohistochemical examination, and scored based on the overall expression of histone H2AX phosphorylated on serine 139 (γH2AX) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Burn wound closure improved in the B1 siRNA-treated group compared with that in the control group, especially from days 14-28 post-injury (P<0.001). The overall pathological score and degree of B1 methylation in the B1 siRNA-treated group improved significantly at days 14-28 post-injury, with the maximum improvement observed on day 14 (P<0.01) compared with the NSS and Ca-P nanoparticle groups. Immunohistochemical staining revealed lower expression of γH2AX and 8-OHdG in the B1 siRNA-treated group than in the control groups at days 14-28 post-injury; the maximum improvement was observed on days 14 and 21. These data imply that administering SINE siRNA is a promising therapeutic option for managing second-degree burns.

Gefitinib-associated lichen planus pigmentosus-like eruption.

The epidermal growth factor receptor (EGFR) signaling pathway is one of the oncogenic pathways in non-small cell lung cancer. Gefitinib is classified as a first-generation EGFR-tyrosine kinase inhibitor (TKI). A variety of cutaneous adverse effects related to the drug has been reported. Cutaneous hyperpigmentation is a rare side effect of EGFR inhibitor (EGFRi). Herein, we report a 62-year-old woman with non-small cell lung carcinoma who presented with symmetrical, slate-gray-to-brownish-black macular pigmentation on sun-exposed and non-sun-exposed areas after eight months of gefitinib administration. The clinical features were consistent with lichen planus pigmentosus. This case highlights the unusual hyperpigmented condition occurring in patients taking EGFR-TKIs.

Methylene blue-mediated photodynamic therapy may be superior to 5% amorolfine nail lacquer for non-dermatophyte onychomycosis.

BACKGROUND: Methylene blue-mediated photodynamic therapy as an antimicrobial has been reported to improve onychomycosis. OBJECTIVES: To compare the short-term efficacy of methylene blue-mediated photodynamic therapy (MB-PDT) and 5% amorolfine nail lacquer (AMO) for toenail onychomycosis using higher intensity and shorter total treatment period than previously reported. METHODS: Twenty-seven toenails with onychomycosis were randomized to receive either six biweekly sessions of MB-PDT or AMO for twelve weeks. Dermoscopic photography was used for onychomycosis severity index assessment under a dermoscopic inspection (d-OSI) at baseline, weeks 6, 10, 14 and 22 as well as microscopic and microbiological tests. Adverse events were recorded. RESULTS: All subjects completed the study. Causative organisms found were exclusively non-dermatophytes including Fusarium spp., Asperillus spp.,and yeasts. Fifteen toenails received MB-PDT, whilst 12 received AMO. D-OSI showed greater improvement in MB-PDT than in AMO groups at weeks 6, 10, 14 as well as 22, with median changes of -2, -3, -4 (P = .055). and - 3 respectively in the MB-PDT group. The AMO group displayed the median d-OSI change of 0 throughout the study period. Mycological cure rate at 22 weeks in MB-PDT and AMO group was 73.3% and 66.67% (P > .05). Clinical cure rate at 22 weeks in MB-PDT (26.7%) was higher than AMO (16.7%), (P > .05). All patients only felt comfortably warm during the MB-PDT treatment. No major adverse events were found in both groups. CONCLUSIONS: MB-PDT appeared to be more efficacious for non-dermatophyte onychomycosis than AMO particularly in a limited period and moderately severe onychomycosis.

Pulsed-dye laser as an adjuvant treatment for discoid lupus erythematosus: a randomized, controlled trial.

PURPOSE: To evaluate the efficacy and safety of pulsed-dye laser (PDL) for discoid lupus erythematosus (DLE) in a double blinded, randomized, controlled fashion. METHOD: Forty-eight DLE lesions from nine patients were recruited. The lesions on one side of the body were randomized into the treatment group and the other side served as a control. Treatments with the PDL (595 nm) were delivered every four weeks for four consecutive months. The patients were evaluated at weeks 0, 4, 8, 12, 16 and 24. Erythema index (EI) and Texture index (TI) were obtained by Antera3D®. Modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) and physician global assessment (PGA) scores were assessed in every visit. Lesional skin biopsies before and after the PDL treatment were taken from four patients. RESULTS: The lesions treated with the PDL demonstrated significantly more decreases in EI, TI and improvement in PGA scores compared to the control. Though there was improvement of mCLASI in the laser group, the significance difference was not observed. Interestingly, real-time polymerase chain reaction showed a reduction in CXCL-9, 10, IFN-γ, IL-1ß, TNF-α and TGF-ß. Additionally, post-treatment DLE lesions demonstrated decreased CD3, CD4, CD8 and CXCR3-positive cells. CONCLUSIONS: Improvements of DLE can be achieved with PDL.

Mutations in γ-secretase subunit-encoding PSENEN underlie Dowling-Degos disease associated with acne inversa.

Dowling-Degos disease (DDD) is an autosomal-dominant disorder of skin pigmentation associated with mutations in keratin 5 (KRT5), protein O-fucosyltransferase 1 (POFUT1), or protein O-glucosyltransferase 1 (POGLUT1). Here, we have identified 6 heterozygous truncating mutations in PSENEN, encoding presenilin enhancer protein 2, in 6 unrelated patients and families with DDD in whom mutations in KRT5, POFUT1, and POGLUT1 have been excluded. Further examination revealed that the histopathologic feature of follicular hyperkeratosis distinguished these 6 patients from previously studied individuals with DDD. Knockdown of psenen in zebrafish larvae resulted in a phenotype with scattered pigmentation that mimicked human DDD. In the developing zebrafish larvae, in vivo monitoring of pigment cells suggested that disturbances in melanocyte migration and differentiation underlie the DDD pathogenesis associated with PSENEN. Six of the PSENEN mutation carriers presented with comorbid acne inversa (AI), an inflammatory hair follicle disorder, and had a history of nicotine abuse and/or obesity, which are known trigger factors for AI. Previously, PSENEN mutations were identified in familial AI, and comanifestation of DDD and AI has been reported for decades. The present work suggests that PSENEN mutations can indeed cause a comanifestation of DDD and AI that is likely triggered by predisposing factors for AI. Thus, the present report describes a DDD subphenotype in PSENEN mutation carriers that is associated with increased susceptibility to AI.

The Efficacy of Gynura pseudochina DC. var. hispida Thv. Ointment in Treating Chronic Plaque Psoriasis: A Randomized Controlled Trial.

BACKGROUND: A recent study showed that Gynura pseudochina DC. var. hispida Thv. leaf extract (GP) can reduce the activation of the nuclear factor κB (NF-κB) pathway and suppress the release of interleukin (IL)-1ß, IL-6, and tumor necrosis factor -α, which play an important role in the pathogenesis of psoriasis. METHODS: Twenty-five patients with mild to moderate plaque psoriasis completed a 4-week trial. Twice daily, they applied the GP ointment on psoriatic lesions on one side of the body, and they applied 0.1% triamcinolone (TA) cream on the other side. The Targeted Area Score (TAS), Psoriasis Severity Index (PSI) scores, and Physician's Global Assessment (PGA) scores were assessed at baseline and at weeks 1, 2, 3, and 4. Pre- and post-treatment skin samples were taken. Phosphorylation of NF-κB p65, Ki-67, and epidermal thickness were analyzed through immunohistochemistry. RESULTS: The TAS for erythema, scaling, and induration and PSI scores decreased on both treated sides. A statistically significant difference was observed beginning at the first week of treatment. The GP ointment significantly decreased scaling scores. However, no significant differences were observed between the TAS for erythema and induration or the PSI and PGA scores. Immunohistochemical staining revealed diminution of phosphorylated NF-κB p65, Ki-67, and epidermal thickness in the lesions treated with the GP ointment. The ointment was well tolerated, with minimal side effects. No laboratory abnormalities were detected. CONCLUSIONS: The GP ointment demonstrated efficacy similar to that of 0.1% TA cream for mild to moderate chronic plaque psoriasis. In addition, its short-term side effects were minimal.

Clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas: the Yale University Spitzoid Neoplasm Repository experience, 1991 to 2008.

BACKGROUND: Spitz nevi and Spitzoid malignant melanomas are uncommon and may be difficult to distinguish histopathologically. Identification of clinical features associated with these lesions may aid in diagnosis. OBJECTIVE: We sought to identify clinical characteristics associated with Spitz nevi and Spitzoid malignant melanomas. METHODS: We conducted a retrospective cohort study of Spitz nevi and Spitzoid malignant melanomas from the Yale University Spitzoid Neoplasm Repository diagnosed from years 1991 through 2008. Descriptive statistics and multivariate logistic regression were used to compare select patient- and tumor-level factors associated with each lesion. RESULTS: Our cohort included 484 Spitz nevi and 54 Spitzoid malignant melanomas. Spitz nevi were more common (P = .03) in females (65%; n = 316) compared with Spitzoid malignant melanomas (50%; n = 27), occurred more frequently in younger patients (mean age at diagnosis 22 vs 55 years; P < .001), and more likely presented as smaller lesions (diameter 7.6 vs 10.5 mm; P < .001). Increasing age (odds ratio 1.16, 95% CI [1.09, 1.14]; P< .001) and male gender (odds ratio 2.77, 95% CI [1.17, 6.55]; P< .02) predicted Spitzoid malignant melanoma diagnosis. LIMITATIONS: Small sample size, unmeasured confounding, and restriction to a single institution may limit the accuracy and generalizability of our findings. CONCLUSIONS: Age and gender help predict diagnosis of Spitz nevi and Spitzoid malignant melanomas.

Expanding phenotypic spectrum of familial comedones.

Familial comedones is a rare autosomal dominant disorder characterized by thousands of comedones developing in teens. Some pits or inflammatory lesions may coexist. Only 32 patients from three families have previously been reported. We report herein 12 cases in two unrelated families with familial comedones. Clinical manifestations among members in the same family vastly vary from scattered comedones on the face, trunk, upper and lower extremities to generalized thousands of open comedones, a large number of skin pits and acneiform inflammatory lesions over the entire body. Additionally, multiple severe purulent nodules and abscesses that leave unsightly scars similar to those of hidradenitis suppurativa are observed. Lesions of long-standing inflammation in two patients had developed into squamous cell carcinoma with a poor prognosis. The phenotypic spectrum of familial comedones varies to a large degree. Most importantly, there is potential for some long-standing inflammatory lesions to develop into squamous cell carcinoma. Extra vigilance in surveillance and prompt treatment for such lesions are recommended.

Generalized dowling-degos disease: case reports.

Dowling-Degos disease (DDD) is a rare autosomal dominant trait characterized by numerous, symmetrical, progressive and pigmented macules over the axillae, groins, face, neck, arms and trunk as well as scattered comedo-like lesions (dark dot, follicles) and pitted acneiform scars. Histopathology is diagnostic testing using a distinctive form of acanthosis, characterized by an irregular elongation of thin branching rete ridges, with a concentration of melanin at the tips. We report cases of generalized DDD in a single family with autosomal dominant penetrance. DDD can be presented in a generalized form with hypopigmented lesions instead of reticulate hyperpigmentation confined to the flexor areas. This form can be differentiated from DUH by histopathology.

Neuropilin-2 as a useful marker in the differentiation between Spitzoid malignant melanoma and Spitz nevus.

BACKGROUND: Spitzoid malignant melanoma (SMM) shares many histopathologic features with Spitz nevus (SN). The distinction between SMM and SN remains one of the most difficult diagnostic problems in dermatopathology. Neuropilin-2 (NRP2) is a cytoplasmic/cell surface protein that is a mediator of melanoma-endothelial cell interaction. OBJECTIVE: The aim of this study was to evaluate NRP2 expression in SMM and SN and to determine whether it can reliably differentiate between the 2 groups. METHODS: We studied the expression of NRP2 in 19 cases of SMM and 19 cases of SN from Yale Spitzoid Neoplasm Repository, New Haven, Conn. RESULTS: All 19 cases of SMM (100%) expressed NRP2. Most SMM showed moderate- and high-intensity staining in the majority of the melanoma cells. Most of the SN (14/19, 74%) were negative for the marker. NRP2 labeled only 5 of 19 SN (26%) and all of them demonstrated mild staining intensity. NRP2(+) staining was statistically significant in differentiating SMM from SN (P < .05). LIMITATIONS: Small study size is a limitation. CONCLUSIONS: NRP2 expression in SMM and SN may be a useful adjunct marker, in addition to histopathologic evaluation, in the differentiation between these 2 entities.

Detecting HPV in cutaneous lesions using anti-HPV antibody immunohistochemistry.

Most condyloma are diagnosed clinically (without a biopsy) or histopathologically (if biopsied) without any ancillary testing. In some cases, additional confirmation of productive infection by human papillomavirus (HPV) or typing of HPV is desired, and in situ hybridization (ISH) is the most commonly used test. However, ISH is not readily available in most laboratories and only detects certain genital subtypes of HPV. The aim of this study was to evaluate the sensitivity and specificity of an anti-HPV antibody, in 25 lesions (both HPV induced and non-HPV induced) mostly from the genital region, with comparison to results with ISH and findings on hematoxylin and eosin staining. The sensitivity and specificity for the anti-HPV antibody used in this study are 90.9% and 85.7%, respectively, compared with ISH. Immunohistochemistry with this anti-HPV antibody, like ISH, was generally positive in cases showing koilocytes/koilocytotic atypia (86%). Immunohistochemical staining also detected productive infection with HPV in 23% (3 of 13) of cases without koilocytes/koilocytotic atypia. Thus, although staining is generally positive in cases with diagnostic findings of koilocytes/koilocytotic atypia in hematoxylin and eosin sections, immunohistochemistry can detect HPV in some cases without koilocytes/koilocytotic atypia.

Expression of p16 alone does not differentiate between Spitz nevi and Spitzoid melanoma.

BACKGROUND: Spitz nevi and Spitzoid melanomas show overlapping histopathologic features, often making the diagnosis challenging. The p16 protein functions as a tumor suppressor and loss of its expression may be seen in some melanomas. METHODS: We evaluated 18 Spitz nevi and 19 Spitzoid melanomas from the Yale Spitzoid Neoplasm Repository for p16 expression. A staining intensity score (SIS) was calculated by multiplying a score for the percentage of stained cells (0-3) by a score for staining intensity (0-3). RESULTS: Staining with p16 was positive in 15/18 (83%) Spitz nevi and 15/19 (79%) Spitzoid melanomas (p = 0.73). Both Spitz nevi and Spitzoid melanomas had a similar SISs, 4.9 and 3.8, respectively (p = 0.057). All 19 patients with Spitzoid melanomas had poor outcome with either death (6 patients) or metastases (13 patients) at a median (3 years) and mean (5.4 years) follow up. In contrast, all 18 patients with Spitz nevi had a benign course with no adverse events at a median (4 years) and mean (4 years) follow up. CONCLUSIONS: We found no significant difference in p16 staining in Spitz nevi and Spitzoid melanomas. We conclude that p16 does not appear to be a useful immunohistochemical marker in distinguishing between Spitz nevi and Spitzoid melanomas.

Myrmecia wart inclusions as an incidental histopathologic finding.

BACKGROUND: Latent infection by human papillomavirus (HPV) has been described for genital (mucosal) and epidermodysplasia verruciformis subtypes. Only rarely has cutaneotropic, non-oncogenic HPV been found by polymerase chain reaction studies in normal skin. METHODS: We noted myrmecia wart inclusions as an incidental histopathologic finding in four specimens from diverse sites (eyebrow, scalp, forehead, leg). The final diagnoses for these four cases were intradermal nevus, scarring alopecia, benign keratosis and stasis dermatitis. Anti-HPV antibody staining was performed in all cases. This antibody detects HPV-1,6,11,16,18 and 31 in formalin-fixed paraffin-embedded tissue. RESULTS: The foci of myrmecia wart inclusions were characterized by smooth to angular cytoplasmic inclusions in the granular layer, spanning one to three rete. The inclusions stained with an anti-HPV antibody in three specimens. CONCLUSIONS: This finding of incidental myrmecia wart inclusions in skin biopsies supports latent infection by cutaneotropic, non-carcinogenic HPV.