Characterization of T-Helper Immune Phenotype in Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Endorses a Delayed-Type Hypersensitivity Reaction.

ABSTRACT: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug eruption with a characteristic distribution of erythema on the gluteal/inguinal region and intertriginous areas with unclear pathogenesis. In this study, we aimed to characterize the T-helper immune phenotype in SDRIFE in comparison with psoriasis and eczema to further the understanding of the pathophysiology and immune response of this rare disorder. Immunohistochemical staining was performed on 9 skin biopsies each from SDRIFE, psoriasis, and eczema using immunohistochemistry for CD3 and dual CD4/T-bet, CD4/GATA3, and CD4/RORC to quantify the percentage of Th1, Th2, and Th17 cells, respectively. A significant difference was detected in the average percentage of Th1 between all 3 groups with the highest percentage of Th1 cells seen in psoriasis, followed by SDRIFE and eczema. SDRIFE showed significantly lower Th2 expression as compared to both psoriasis and eczema. There was a trend towards a higher average percentage of Th17 in psoriasis and SDRIFE, and the ratio of Th17:Th2 was significantly higher in samples of SDRIFE compared with both eczema and psoriasis. The findings characterize SDRIFE as a Th1 and possibly Th17-driven process, which could inform future therapeutic options and substantiate the model of SDRIFE as a delayed-type hypersensitivity reaction.

Use of Cytokeratin 17 in the Differentiation Between Desmoplastic Trichilemmoma and Cutaneous Basal Cell Carcinoma.

ABSTRACT: Desmoplastic trichilemmoma (DTL) is a variant of trichilemmoma characterized by a prominent desmoplastic stroma that may mimic invasive carcinoma. These lesions typically show features of a conventional trichilemmoma at the periphery, surrounding dense hyalinized stroma with entrapped cords of tumor cells. On a small or superficial biopsy, DTL may pose a diagnostic challenge in distinguishing this benign adnexal neoplasm from invasive carcinoma, particularly basal cell carcinoma (BCC). We aimed to investigate whether the immunohistochemical expression of cytokeratin 17 (CK17) would be useful in the differentiation between DTL and BCC. CK17 is expressed in normal adnexal structures and has been shown to demonstrate strong staining in BCCs. Expression of CK17 was examined in 23 cases of DTL and 23 BCCs. An immunoreactivity score was assigned using the percentage of tumor cells staining with scoring as follows: 0, complete negativity; 1, < 15% tumor cells staining; 2, 15%-84% tumor cells staining; and 3, >85% staining. All cases of BCC scored as 3, whereas 18% of DTL scored as 3. The mean percent staining for CK17 was significantly higher for BCCs (97% of tumor cells) than DTLs (57% of tumor cells); P < 0.001 in the unpaired t test. The pattern of CK17 staining may also help differentiate between cases scoring 3. All BCCs showed strong diffuse staining throughout, whereas for those cases of DTL with a score of 3, the peripheral basaloid rim in the tumor lobules did not stain. CK17 is a useful adjunct in distinguishing DTL from BCC in small or superficial biopsy specimens.

Symmetric drug-related intertriginous and flexural exanthema: Clinicopathologic study of 19 cases and review of literature.

BACKGROUND: Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE. METHODS: Pathology archives were searched for "SDRIFE" and "baboon syndrome." Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. RESULTS: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." CONCLUSIONS: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics.

Calciphylaxis-Associated Cutaneous Vascular Calcification in Noncalciphylaxis Patients.

Calciphylaxis is a highly morbid disease that is strongly associated with chronic kidney disease (CKD); however, the histologic criteria for diagnosis have not been well established nor have their specificity for calciphylaxis been determined. This retrospective study aimed to examine the prevalence of histologic features commonly associated with calciphylaxis in noncalciphylaxis patients. We also sought to evaluate whether these features may be more prevalent in patients with CKD. To assess this, healthy marginal skin tissue from above-the-knee amputation specimens was compared between patients with CKD (n = 23) and without CKD (n = 47). Intravascular calcification of capillaries or small-to-medium arterioles was detected on von Kossa stain in 40.0% of the entire cohort. Capillary calcification and intravascular thrombosis were more prevalent in patients with CKD. Finely stippled capillary calcification was present in 26.1% of patients with CKD versus 8.5% of patients without CKD (P = 0.0484), and intravascular thrombosis was present in 8.7% of patients with CKD and 0.0% of patients without CKD (P = 0.0403). None of the patients in this study had clinical evidence of calciphylaxis at presentation and in at least a 1-year follow-up period. This study confirms that the histologic features previously associated with calciphylaxis are nonspecific and are more prevalent in patients with CKD.

Wnt Signaling Pathway Proteins in Scar, Hypertrophic Scar, and Keloid: Evidence for a Continuum?

Hypertrophic scars and keloids are fibroproliferative lesions characterized by excessive collagen deposition. It is unclear whether these entities represent distinct disorders or share a common pathogenesis and the molecular underpinnings of these lesions are poorly understood. Accumulating evidence suggests that the Wnt signaling pathway is a key regulator of wound healing. In this study, tissue microarray was used to evaluate the protein expression profile for Wnt3a, phosphorylated glycogen synthase kinase 3 alpha (pGSK-3α), WNT1-inducible-signaling pathway protein 1 (WISP1), and WISP2 in normal skin, scars, hypertrophic scars, and keloids. Analysis revealed significantly increased fibroblast expression of pGSK-3α in scars (27.2%), hypertrophic scars (30.4%), and keloids (57.3%) compared with normal skin (16.4%) (all differences statistically significant; P < 0.01). Analysis of WISP2 showed 94% of fibroblasts in normal skin expressing WISP2 and significantly decreased expression in scars (46.8%), hypertrophic scars (27.0%), and keloids (61.3%) (all differences statistically significant; P < 0.01). The parallel patterns of expression of pGSK-3α and WISP2 in scars and hypertrophic scars and significantly increased expression in keloids may support the notion that keloids are a truly distinct fibrosing disorder and may provide further evidence for targeting the Wnt signaling pathway in the treatment of keloids.

Correlation between clinical and pathological features of cutaneous calciphylaxis.

Calciphylaxis is a rare and life-threatening disease that classically manifests with painful skin lesions. It occurs mainly in patients with end-stage renal disease (ESRD) treated with dialysis, has poor outcomes, and has no FDA-approved treatment. Our cohort study aims to examine the clinical and pathological features of calciphylaxis and investigates the correlation between cutaneous clinical manifestations and histopathological findings. Data from 70 calciphylaxis patients who were evaluated at the Massachusetts General Hospital between January 2014 and April 2018 were collected from the institutional electronic database. The median age was 58 years (interquartile range [IQR]: 49-69 years), 60% were women, and 73% were of white race. Most (74%) patients reported severe pain at the time of calciphylaxis diagnosis with a median pain intensity score of 8/10 (IQR: 6-10) on a 0-10 pain scale. The median time from symptom onset to clinical diagnosis was 9 weeks (IQR: 6-16 weeks). The majority (87%) of patients presented with open necrotic wounds (advanced stage lesion) at the time of diagnosis. Common cutaneous clinical features included ulceration (79%), induration (57%), and erythema (41%), while common pathological features included cutaneous microvascular calcification (86%) and necrosis (73%). The presence of fibrin thrombi in skin biopsies was associated with pain severity (p = 0.04). The stage of a skin lesion positively correlated with the presence of necrosis on histological analyses (p = 0.02). These findings have implications for improving understanding of calciphylaxis origins and for developing novel treatments.