Insights into Lichen Planus Pigmentosus Inversus using Minimally Invasive Dermal Patch and Whole Transcriptome Analysis.

Lichen Planus Pigmentosus inversus (LPPi) is a rare interface and lichenoid dermatitis (ILD) and supposed variant of lichen planus (LP) that presents as well-demarcated brown to grey macules in flexural and intertriginous areas. LPPi is deemed 'inversus' because its anatomical distribution in skin folds is opposite that seen in lichen planus pigmentosus (LPP) whose pigmented lesions arise on sun-exposed skin. Biopsy is required for the clinical diagnosis of all ILDs. Though multiple clinically-oriented studies have reported differences between LPP, LPPi, and LP, few molecular studies have been performed. In this case study, 3 patients, 2 with LPPi and one with LP, provided samples using minimally invasive whole transcriptome analysis using a dermal biomarker patch. This study confirms the involvement of interferon signaling and T-cell activation in LPPi and suggests an expression profile distinct from LP. Specific genes significantly upregulated in LPPi vs LP include an intergenic splice variant of the primary pigmentation determining receptor in humans and dysregulation of genes essential for ceramide synthesis and construction of the cornified envelope. This work expands upon our knowledge of the pathogenesis of LPPi vs LP, and supports the potential use of this technology in the diagnostic clinical setting to mitigate the need for invasive procedures.

Chondrodermatitis Nodularis Nasi: A Case Report of a Rare Variant of Chondrodermatitis Nodularis Helicis.

ABSTRACT: Chondrodermatitis nodularis helicis is an inflammatory condition affecting the helix or antihelix of the ear. It is commonly described as a solitary, painful, ulcerated nodule affecting the cartilage or skin because of continuous pressure, trauma, sun exposure, or ischemic changes. In this case report, we present a rare variant of chondrodermatitis, named chondrodermatitis nodularis nasi, which affects the skin and cartilage of the nose. Clinical resemblance to neoplasms of the skin such as squamous cell carcinoma and basal cell carcinoma requires that a biopsy be performed for definitive diagnosis. On histopathological examination, chondrodermatitis presents as a central ulcer bordered by epidermal hyperplasia, hypergranulosis, hyperkeratosis, and parakeratosis with fibrin deposits in the papillary dermis admixed with sparse inflammatory cells. Included in this case report is a discussion of the clinical and histopathology of chondrodermatitis nodularis nasi. With increased frequency of diagnosing this rare variant, better management and treatments can be explored.

ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers.

BACKGROUND: p63, a member of the p53 gene family, is an important regulator for epithelial tissue growth and development. ∆Np63α is the main isoform of p63 and highly expressed in Non-melanoma skin cancer (NMSC). Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose biochemical features and cellular regulation are distinct from those of conventional MAPKs such as ERK1/2. While ERK3 has been shown to be upregulated in lung cancers and head and neck cancers, in which it promotes cancer cell migration and invasion, little is known about the implication of ERK3 in NMSCs. METHODS: Fluorescent immunohistochemistry was performed to evaluate the expression levels of ΔNp63α and ERK3 in normal and NMSC specimens. Dunnett's test was performed to compare mean fluorescence intensity (MFI, indicator of expression levels) of p63 or ERK3 between normal cutaneous samples and NMSC samples. A mixed effects (ANOVA) test was used to determine the correlation between ΔNp63α and ERK3 expression levels (MFI). The regulation of ERK3 by ΔNp63α was studied by qRT-PCR, Western blot and luciferase assay. The effect of ERK3 regulation by ΔNp63α on cell migration was measured by performing trans-well migration assay. RESULTS: The expression level of ∆Np63α is upregulated in NMSCs compared to normal tissue. ERK3 level is significantly upregulated in AK and SCC in comparison to normal tissue and there is a strong positive correlation between ∆Np63α and ERK3 expression in normal skin and skin specimens of patients with AK, SCC or BCC. Further, we found that ∆Np63α positively regulates ERK3 transcript and protein levels in A431 and HaCaT skin cells, underlying the upregulation of ERK3 expression and its positive correlation with ∆Np63α in NMSCs. Moreover, similar to the effect of ∆Np63α depletion, silencing ERK3 greatly enhanced A431 cell migration. Restoration of ERK3 expression under the condition of silencing ∆Np63α counteracted the increase in cell migration induced by the depletion of ∆Np63α. Mechanistically, ERK3 inhibits the phosphorylation of Rac1 G-protein and the formation of filopodia of A431 skin SCC cells. CONCLUSIONS: ERK3 is positively regulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in NMSC.

Coronavirus (COVID-19) Infection-Induced Chilblains: A Brisk Perieccrine Inflammatory Response.

ABSTRACT: The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection-induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection-induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.

Clopidogrel-associated vasculopathic cutaneous reaction.

We present a case report of a man who experienced vascular thromboses, which subsequently resolved following discontinuation of clopidogrel.

Clear cell acanthoma: a rare clinical diagnosis prior to biopsy.

BACKGROUND: Clear cell acanthoma is a rare, benign epidermal tumor with a clinical hybrid appearance and a distinct histological one. It is frequently mistaken for other clinical lesions. OBJECTIVE: To evaluate the frequency that clear cell acanthoma was listed in the clinical differential diagnosis of histologically confirmed specimens. METHODS: A regional dermatopathology lab database was evaluated from January 1998 through March 2008 for histologically diagnosed cases of clear cell acanthoma. Clinical data that was submitted with these cases including differential diagnoses was analyzed. RESULTS: During this time period of review, 411 histologically confirmed cases of clear cell acanthoma were identified. This entity was listed as a diagnostic possibility in 11 (2.7%) of the cases. CONCLUSION: Clear cell acanthoma was rarely listed amongst the differential diagnosis of biopsy proven specimens. This may be due to a variable clinical appearance with overlapping features of several other lesions making it difficult to distinguish, or an entity that is rare and not frequently suspected. Additional studies with dermatoscopy may help to further delineate the reasons for the low diagnostic sensitivity.

Granulomatous pigmented purpura: an unusual histological variant.

Pigmented purpuric dermatoses (PPDs) tend to vary clinically, yet share a similar histology. Granulomas are only rarely seen, with 4 prior reported cases, designated granulomatous pigmented purpura. Historically, granulomatous pigmented purpura has been seen in Asians. In this article, we report the case of a 42-year-old, white female with granulomatous pigmented purpura, the fifth such reported case in the literature. Histopathological examination revealed a granulomatous dermatitis with eosinophils, extravasated erythrocytes, melanophages, and vascular proliferation. These findings were consistently reported on subsequent biopsy 6 months later. This case illustrates a rare histological finding in PPDs. Medications associated with PPD are reviewed and the patient's use of mesalamine and balsalazide for ulcerative colitis are deemed potential triggers, given their relative similarity to aspirin, a known trigger of PPD. Although other granulomatous processes must be excluded in such patients, one must consider the possibility of granulomatous pigmented purpura in the appropriate setting.

Histological changes occurring after endoluminal ablation with two diode lasers (940 and 1319 nm) from acute changes to 4 months.

BACKGROUND: Endovenous laser ablation of the saphenous vein was studied from a histologic analysis to establish changes that occur from time of injury to 4 months when the vein is difficult to visualize by ultrasound. METHODS: Twenty-four patients were examined after treatment with either a 1319 nm diode laser (Sciton, Palo Alto, CA) or a 940 nm diode (Dornier, Kennasaw, GA) 12 patients were randomly assigned to the 940 nm group and 12 patients to the 1319 nm group. Histologic evaluations were only done once per patient. All patients had symptomatic saphenous insufficiency with varicosities. All were in CEAP class 3 or 4. Sections of treated veins were submitted for evaluation after staining with hematoxylin-eosin. The evaluations were done acutely, at 1 and 4 months. Ultrasound findings were also evaluated and compared at the same intervals. RESULTS: Acutely, all examined veins revealed loss of intima. In the 1319 nm group numerous vacuoles were present in the subintimal layer. On gross exam at 1 month, both groups showed vein wall thickening, intraluminal thrombus and inflammatory changes. Histologic evaluation showed thrombus was present with many fibroblasts and inflammatory cells. At 4 months, collagen was the predominant histologic finding. However, the changes were less in regards to the injury response with the 1,319 nm group as manifested by less collagen deposition at 4 months. CONCLUSION: This study demonstrates the cellular sequence that occurs after endovenous ablation. Fibroblast infiltration is a result of the injury response which leads to negative modeling of the thrombus and eventual collagen deposition. Replacement of the thrombus with collagen is necessary for eventual long-term success.

Laser-assisted tattoo removal with topical 5% imiquimod cream.

BACKGROUND: Laser-assisted tattoo removal is effective but can be costly and time-consuming and can result in disfiguring scars and pigment alterations. Imiquimod, an immune response modifier, may play a role in tattoo removal. OBJECTIVE: The objective was to evaluate the safety and efficacy of topical 5% imiquimod cream used daily in conjunction with laser therapy to remove unwanted tattoos. MATERIALS AND METHODS: Twenty subjects with two similar tattoos were enrolled in this randomized, prospective, double-blinded, case-controlled study. Tattoos were treated with either imiquimod or placebo daily and laser therapy every 4 to 6 weeks for a total of six sessions. The primary efficacy parameter was tattoo clearance (5-point scale, poor through complete). Secondary efficacy parameters included textural changes (5-point scale, minimal through severe), pain during and between laser procedures, and undesirable pigment alterations. RESULTS: Nineteen subjects completed the study. The mean score for tattoo clearance with imiquimod versus placebo was 3.2 versus 2.9 and, for textural changes, was 1.37 versus 1.21 (differences not statistically significant). There was no difference in subjective pain during and between laser sessions and no undesirable pigment alterations were reported. Adverse reactions were more frequent with imiquimod compared to placebo. CONCLUSION: Topical imiquimod is an ineffective adjunct to laser-assisted tattoo removal.

940-nm laser for treatment of saphenous insufficiency: histological analysis and long-term follow-up.

OBJECTIVE: Currently, many methods are available for the treatment of saphenous insufficiency. Modalities available include surgery, sclerotherapy, and radiofrequency closure. Recently, a method has been introduced using laser energy for the treatment of the saphenous vein using a bare-tipped fiber. Our experience using the 940-nm wavelength forms the basis of this report. METHODS: Indications for treatment with laser obliteration alone was saphenous insufficiency, a saphenofemoral junction of less than 15 mm in diameter and absence of concurrent anticoagulation therapy. Ninety-two percent of the patients were in Class C-2 to C-4, and 8% were in C-5 to C-6. Eight percent had a concurrent high ligation of the saphenous vein. Fifteen patients were treated at varying energy levels and time durations for saphenous insufficiency using a bare-tipped fiber and the 940-nm wavelength laser (SkinPulse S by Dornier). These patients then had histologic evaluation of the treated vein. An additional 620 patients were subsequently treated for saphenous insufficiency using the 940- nm wavelength laser. RESULTS: At 1-sec pulse durations, histologic studies reveal endothelium and subendothelial damage as the initial response to laser damage. At 3 months, endothelium was still absent, with organized thrombus in the lumen. At 6 months, at 1-sec pulse duration, thrombus organization was still present with evidence of muscle wall damage. Ultrasound evaluation revealed gradual diminution in saphenous vein diameter over 6 months, with absence of reflux and normal flow at the saphenofemoral junction in 95% of patients. For pulse durations of greater than 1 sec, there was transmural injury. CONCLUSION: Laser treatment of the saphenous vein was associated with no complications in our series of patients. The vein remained closed in 95% of those treated. This technique may replace other treatment modalities in up to 90% of patients.

Cyclosporine-induced folliculodystrophy.

We describe a 34-year-old kidney transplant patient who developed a distinct cutaneous side-effect to cyclosporine manifested as an infiltrated appearance to the skin with abundant flesh-colored, follicular papules predominantly affecting the ears, nose, and surrounding areas of the face, but also the trunk and extremities. The clinical and histologic findings in this case closely match those presented in 2 previous case reports, in which immunosuppressive doses of cyclosporine appeared to be causative. We present a detailed report of the clinical and histologic findings that are unique to these 3 cases and we introduce a theory, based on the recent in vitro studies involving cyclosporine, to help explain the pathogenic events induced by cyclosporine in these patients. We propose the term "cyclosporine induced folliculodystrophy" or CIF as an appropriate name for this distinct clinicohistopathologic entity. Finally, we set forth 3 clinical and 4 histopathologic criteria upon which the diagnosis of CIF can be made.