Cicatricial pemphigoid Brunsting-Perry variant masquerading as neutrophil-mediated cicatricial alopecia.

A 72-year-old male presented with scarring alopecia on the scalp vertex, multiple crusted plaques on the hairline, and a history of vesicular eruption on the face. The scalp showed crusted plaques with loss of follicular ostia. No follicular pustules or compound follicles were present. An initial transverse scalp biopsy showed perifollicular neutrophils, lymphocytes, and plasma cells along with dermal fibrosis. Focal epidermal/dermal and follicular/adventitial dermal clefts were apparent but were thought to be secondary to fibrosis, and the biopsy result was interpreted to represent a neutrophil-mediated cicatricial alopecia. Concurrently, direct immunofluorescence (DIF) analysis showed linear junctional deposition of IgG and C3. A repeat scalp biopsy revealed more prominent epidermal/dermal clefts, fibrosis, mixed infiltrate with neutrophils, lymphocytes, histiocytes, and plasma cells, as well as prominent follicular/adventitial dermal clefts with perifollicular neutrophils. Given the combination of clefts, perijunctional neutrophils, and positive DIF findings, it became clear that this eruption represented the Brunsting-Perry variant of cicatricial pemphigoid. Here, we illustrated that a neutrophil-rich form of cicatricial pemphigoid can masquerade as a neutrophil-mediated scarring alopecia. In evaluating a specimen suspected to be a neutrophil-mediated scarring alopecia, one should be alert to the presence of subepidermal and perifollicular clefting, and consider cicatricial pemphigoid.

Angina bullosa haemorrhagica-like lesions in pemphigus vulgaris.

BACKGROUND/OBJECTIVES: The aim of this study was to describe a previously unreported association of oral pemphigus vulgaris with short-lived blood-filled painless blisters resembling angina bullosa haemorrhagica (ABH). METHODS: A cross-sectional study of consecutive patients with Pemphigus vulgaris. All patients were examined for the presence of ABH-like lesions, and demographic, clinical and histopathological data were collected. Histopathological examination was performed when feasible. RESULTS: A total of 318 with pemphigus vulgaris were included (63.5% female, mean age: 46 years). ABH-like lesions were present in 82 (25.8%) patients, commonly observed in the buccal mucosa (47, 57.3%) followed by the palate (15, 18.3%). All patients had normal platelet counts with no evidence of bleeding diathesis. Biopsies of the ABH-like lesions showed suprabasal clefts in four of six samples. ABH-like lesions were significantly associated with partial remission of pemphigus vulgaris (47.5%, P = 0.002) and the use of intraoral steroids (P = 0.001, odds ratio: 5.9 [95% confidence interval: 2.5-13.6]). CONCLUSION: ABH-like lesions may represent a transient or abortive form of oral pemphigus vulgaris and tend to have a benign and self-limiting nature.

Characterization of the peripheral neuropathy associated with brentuximab vedotin treatment of Mycosis Fungoides and Sézary Syndrome.

Chemotherapy-induced peripheral neuropathy (CIPN) is common, frequently limits chemotherapy dosing, and negatively impacts quality of life. The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0, and the Total Neuropathy Score clinical version (TNSc) are both validated scores to quantify peripheral neuropathy (PN), with the TNSc being more sensitive to clinical changes. Mycosis fungoides and Sézary syndrome (MF/SS) are characterized by a chronic course, where current therapies are generally non-curative and treatment toxicities have the potential for significant lasting effects. Brentuximab vedotin (BV) is an antibody-drug-conjugate composed of an anti-CD30 monoclonal antibody linked to the microtubule-disrupting agent, monomethyl auristatin E, with a known associated CIPN. In our phase II clinical trial of BV in MF/SS, 25 (69%) of 36 patients developed PN, with 18 (50%) developing Clinically Significant PN, CTCAE v4.0 grade 2 or higher. The median time to grade 2 PN was 15 weeks (range 0.4-48) after the initial dose. By Kaplan-Meier calculation, the median time to improvement from Clinically Significant PN was 30 weeks from the last BV dose. Seventy-four percent had improvement by 24 months. We found that TNSc scores significantly correlated with CTCAE grade, with Spearman correlation coefficient 0.68 (p < 0.001). By logistic regression, for each 100 mg increase in BV total dose, the likelihood of developing Clinically Significant PN increased by 23% (95% CI 4-46%). Improved monitoring of CIPN associated with BV is of paramount importance in the MF/SS population.

Trauma-induced pemphigus: a case series of 36 patients.

BACKGROUND AND OBJECTIVES: Pemphigus is a group of autoimmune diseases characterized by intraepidermal acantholytic blisters. Isomorphic responses, or Koebner phenomenon (KP), defined as the appearance of typical lesions of a disease following trauma are rarely reported in pemphigus. Our aim was to present patients who developed new pemphigus lesions as a result of skin trauma. PATIENTS AND METHODS: The medical files of pemphigus patients from the Autoimmune Bullous Diseases Research Center, who had a history of trauma before the onset or flare of their disease, between 1999 and 2013 were reviewed. RESULTS: Thirty-six pemphigus vulgaris (PV) patients had a history of trauma. Thirteen patients developed new-onset PV and the other 23 had previously been diagnosed with PV. Pemphigus lesions developed most often following major surgeries including abdominal, orthopedic, and chest surgeries as well as dental procedures, blunt physical trauma, and skin surgeries. Moreover, post-cataract laser surgery, burns, radiation therapy, and physiotherapy were also shown to induce pemphigus. Mean time between trauma and lesions was 4.7 weeks for recurrent PV and 15.0 weeks for new-onset PV. CONCLUSIONS: Unnecessary surgery and blunt trauma should be avoided in pemphigus patients. Furthermore, posttraumatic pemphigus should be suspected in poorly healing surgical wounds and confirmatory biopsies are mandatory.

Keratosis Pilaris-Like Reaction Associated With Chromatin Remodeling Complex Inhibition in Uveal Melanoma.

This case series describes a constellation of novel adverse reactions in 3 of 9 patients with uveal melanoma receiving treatment targeting activity of the Brahma-associated factor chromatin remodeling complex.

Epigenetically Enhanced PDT Induces Significantly Higher Levels of Multiple Extrinsic Pathway Apoptotic Factors than Standard PDT, Resulting in Greater Extrinsic and Overall Apoptosis of Cutaneous T-cell Lymphoma.

Aminolevulinate-based photodynamic therapy (ALA-PDT) selectively eliminates diseased tissues primarily through the induction of intrinsic apoptotic pathway. ALA-PDT is a first-line therapy for actinic keratosis, however, it is less effective for cutaneous T-cell lymphoma (CTCL). We have previously demonstrated that the resistance of CTCL to apoptosis correlates with decreased expression of death receptors such as FAS, and that methotrexate functions as an epigenetic regulator that reestablishes the susceptibility of CTCL to extrinsic pathway apoptosis. We showed previously that MTX augments the effectiveness of PDT by sensitizing cells to apoptosis by induction of apoptotic factors, a process we call "epigenetically enhanced" PDT (ePDT). Here, in CTCL cell lines, leukemic CTCL cells, and normal blood T cells, we analyzed multiple components of the FAS, TRAIL, and TNF families using multispectral imaging of immunostained cytopreparations, a quantitative technique with five-fold greater sensitivity than standard immunocytology. ePDT induced significantly greater FAS, FASL, TRAIL-R1 & -R2, and TNFα levels than standard PDT. This correlated with significantly greater induction of extrinsic pathway apoptosis and/or overall apoptosis in all CTCL samples. There was no appreciable effect on normal T cells. These data set the stage for clinical trials of ePDT as a novel localized treatment of CTCL.

Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors.

Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4+ T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

De Sanctis-Cacchione syndrome: A case report and literature review.

De Sanctis-Cacchione (DSC) syndrome is one of the rarest, most severe forms of xeroderma pigmentosum (XP). These patients with XP are of short stature, have mental disabilities, and develop progressive neurologic degeneration because of a severe inability to repair damaged DNA. Herein, we will present the case of a 9-year-old boy who had DSC syndrome with microcephaly, severe psychomotor retardation, ataxia, and hearing loss. The cutaneous manifestations included giant squamous cell carcinoma (SCC) that covered the eye, multiple facial SCCs, and pigment changes on sun-exposed areas. In addition, we include a review of reported rare cases and a brief discussion of disease management.

Pemphigus disease activity measurements: pemphigus disease area index, autoimmune bullous skin disorder intensity score, and pemphigus vulgaris activity score.

IMPORTANCE: Recently, the clinical pemphigus disease activity indexes of Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), and Pemphigus Vulgaris Activity Score (PVAS) were validated to correlate with physician global assessment. The antidesmoglein (anti-Dsg) autoantibodies are known to correlate mostly with pemphigus disease activity. The correlation between these indexes and anti-Dsg1 and anti-Dsg3 enzyme-linked immunosorbent assay values has not been previously evaluated. OBJECTIVES: To evaluate the PDAI, ABSIS, and PVAS in a large number of patients with pemphigus vulgaris and to compare the interrater reliability of these indexes and the convergent validity according to anti-Dsg values. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was performed in 2012 in a referral university center for autoimmune bullous diseases. One hundred patients with confirmed diagnoses of pemphigus vulgaris and clinical pemphigus lesions (mean [SD] age, 43.3 [1.7] years; age range, 14-77 years; female-male ratio, 1:3) were studied. Three dermatologists familiar with immunobullous diseases and the indexes rated the patients. INTERVENTIONS: All 100 patients were evaluated with the PDAI, ABSIS, and PVAS. Three dermatologists independently rated all 3 indexes for each of the patients on the same day. Serum anti-Dsg1 and anti-Dsg3 enzyme-linked immunosorbent assay values were measured simultaneously. MAIN OUTCOMES AND MEASURES: Analyses of interrater reliabilities, convergent validities according to anti-Dsg titers, correlation between the distribution and types of lesions with disease activity, predictors of higher titers of antibody (multiple regression analysis), and cutoff values of measures for 2 titers of anti-Dsg with optimal area under the curve, sensitivity, and specificity were performed. RESULTS: The interrater reliabilities were highest for the PDAI, followed by the ABSIS and the PVAS (intraclass correlation coefficients of 0.98 [95% CI, 0.97-0.98], 0.97 [95% CI, 0.96-0.98], and 0.93 [95% CI, 0.90-0.95], respectively). The convergent validity was highest for the PDAI, followed by the PVAS and the ABSIS (Spearman ρ = 0.67, 0.52, and 0.33, respectively). Head, neck, and trunk involvement were predictors of higher titers of anti-Dsg1. CONCLUSIONS AND RELEVANCE: Among the 3 studied indexes, the PDAI had the highest validity and is recommended for use in multicenter studies for rare diseases, such as pemphigus vulgaris.

Clinicopathological study of 1016 consecutive adnexal skin tumors.

Adnexal tumors (ATs) are primary skin tumors with benign or rarely, malignant behavior. They have been classified based on differentiation towards hair follicle, sebaceous, apocrine or eccrine gland. Few large-scale studies have focused on ATs. To determine the prevalence of ATs and to assess clinical and histopathological trend of ATs. A retrospective descriptive study of all ATs diagnosed in Razi hospital between 2006 and 2010 was performed. A total of 30,000 pathology records were reviewed, and 1016 ATs were included. The prevalence of ATs was 3.3%. 518 patients (51%) were female, with a mean age of 34.5 years. 953 tumors (93.8%) were benign. ATs were most commonly located in the head and neck area (822, 83.5%). The most common histopathological origin of ATs was sebaceous gland (536, 52.7%). Sebaceous nevus of Jadassohn was the most prevalent single tumor type (40.6% of all ATs). In 63.6% (646) of tumors, ATs were clinically suspected by the clinician prior to biopsy. The most common malignant AT was sebaceous carcinoma (23, 36.5% of all malignant ATs). ATs are infrequent lesions, most commonly occurring in 3rd and 4th decade of life. Diagnosis of ATs is made by histopathological studies as they often express indistinctive clinical features. Malignant ATs are rare, occur at an older age, and are often hard to recognize clinically.

Pemphigus vulgaris activity score and assessment of convergent validity.

Pemphigus is a rare autoimmune blistering disease with different phenotypes. The evaluation of therapeutic interventions requires a reliable, valid and feasible to use measurement. However, there is no gold standard to measure the disease activity in clinical trials. In this study we aimed to introduce the pemphigus vulgaris activity score (PVAS) measurement and to assess the convergent validity with the experts' opinion of disease activity. In PVAS scoring, the distribution of pemphigus vulgaris antigen expression in different anatomical regions is taking in to account with special consideration of the healing process. PVAS is a 0-18 scale, based on the extent of mucocutaneous involvement, type of lesion and the presence of Nikolsky's sign. The sum of the scores of total number of lesions, number of different anatomic regions involvement and Nikolsky's sign is weighted by the type of lesion. In the present study, PVAS was assessed in 50 patients diagnosed with pemphigus vulgaris by one dermatologist. Independently, five blinded experts scored all the patients through physician's global assessment (PGA). The convergent validity with experts' opinion was assessed. The Spearman coefficient of correlation showed the acceptable value of 0.751 (95%CI: 0.534- 0.876). PVAS is a valid, objective and simple-to-use scoring measurement. It showed a good correlation with PGA of pemphigus disease activity in Iranian patients with pemphigus vulgaris.

Urological manifestations of sacral agenesis.

OBJECTIVE: To evaluate urologic manifestations of sacral agenesis (SA) and their association with bony defects. METHODS: Urological manifestations of SA were investigated in 50 patients referred to the urology or neurosurgery department. Urologenital signs and symptoms were assessed and a complete history of previous surgical procedures was attained. Plain lumbosacral radiography, abdominal/pelvic ultrasound, voiding cystourethrogram and urodynamic study were evaluated if available. RESULTS: The most common urologic complaints were urinary incontinence and/or constant dribbling, seen in 30 (85%) of 35 children aged 4 years and over. Recurrent urinary tract infection, the second most common, was seen in 37 (74%). Vesicoureteral reflux was identified in 32 (65.3%) patients, 19 (59.3%) were found to have high maximal voiding pressures and post-voiding residual urine was notable in 42 (85.7%). Abnormal urodynamic parameters were found to be consistent with a neurogenic bladder in all patients. Cases were divided into upper motor lesions (in 34) and lower motor disorders (in 15). There was no statistically significant correlation for any GU finding with type of bony aplasia or motor neuron lesion (P = 0.338). CONCLUSION: Voiding impairment and VUR together with recurrent UTI, especially in children with associated renal anomalies, contribute to renal damage. Urinary incontinence with associated social problems frequently occurs in patients with SA. Considering the devastating consequences of this disease in the urinary tract, timely diagnosis, thorough evaluation and appropriate intervention are essential.

Neurological presentations, imaging, and associated anomalies in 50 patients with sacral agenesis.

BACKGROUND: Sacral agenesis is an uncommon congenital disorder that involves multiple organs. OBJECTIVE: We studied neurological manifestations of the disease, common associated disorders, and their relation with extent of bony malformation. METHODS: We investigated neurological manifestations of 50 patients with sacral agenesis. Patients were evaluated for previous procedures, ambulation, limb abnormalities, vertebral alignment, recurrent urinary tract infection, urinary incontinence, dribbling, dimple, lower extremities weakness, myelomeningocele (MMC), and lipomyelomenangocele. RESULTS: Weakness of lower extremities was seen in 37 (74%) patients. Concurrent weakness of proximal and distal muscles of the lower limb was statistically associated with a type of bony aplasia (P = .001). However, paraplegia was seen in only 2 of 44 children over the age of 1, and the rest could walk. Myelodysplastic syndromes were seen in 21 patients. Sacral agenesis is diagnosed in children with concomitant MMC at younger ages and reveals more severe symptoms. Progression of neurological disorders was seen in 19 patients, in all of whom MRI showed tethering of the spinal cord. Urinary disorders including diurnal urinary incontinence (in 30 of 35 children over age 4) and recurrent urinary tract infections (in 37) were also common. Imperforate anus was seen in 11 patients. Twelve children over age 4 reported fecal incontinence, a problem that had statistically significant association with imperforate anus (P = .013). CONCLUSION: Different disorders can concurrently affect patients with sacral agenesis that may have profound impressions on patients and their families. Early diagnosis, thorough evaluation, and proper intervention are of utmost importance as they can prevent or lessen future complications.