Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.

Pemphigus oral lesions area index (POLAI): A new scoring scale for assessing oral pemphigus vulgaris.

OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.

The Promising Role of Polyphenols in Skin Disorders.

The biochemical characteristics of polyphenols contribute to their numerous advantageous impacts on human health. The existing research suggests that plant phenolics, whether consumed orally or applied directly to the skin, can be beneficial in alleviating symptoms and avoiding the development of many skin disorders. Phenolic compounds, which are both harmless and naturally present, exhibit significant potential in terms of counteracting the effects of skin damage, aging, diseases, wounds, and burns. Moreover, polyphenols play a preventive role and possess the ability to delay the progression of several skin disorders, ranging from small and discomforting to severe and potentially life-threatening ones. This article provides a concise overview of recent research on the potential therapeutic application of polyphenols for skin conditions. It specifically highlights studies that have investigated clinical trials and the use of polyphenol-based nanoformulations for the treatment of different skin ailments.

ODSS vs. ABSIS and PDAI oral parts in pemphigus vulgaris: inter-rater reliability and testing times.

OBJECTIVES: The existence of standard methods for diagnosis and measuring the severity of diseases leads to a more accurate severity assessment, the possibility of following up, and the possibility of comparing the results of studies. This study aimed to compare different pemphigus vulgaris (PV) assessment methods regarding inter-observer reliability and testing times-focusing on oral parts. MATERIALS AND METHODS: Two dermatologists evaluated orally involved PV patients by oral parts of Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), Pemphigus Disease Area Index (PDAI), and Oral Disease Severity Score (ODSS). RESULTS: Seventy patients completed the study. The intraclass correlation coefficient showed the evaluators' agreements on ABSIS, PDAI, and ODSS with 0.98, 0.94, and 0.95, respectively. Reliability analyses showed near-perfect relationships between each scoring methods pairs. There was no association between lesion sites and disease severity. The PDAI scoring duration was significantly shorter, and the ABSIS scoring duration was significantly longer. CONCLUSION: ODSS is valid for evaluating oral involvement in patients with PV and relates to ABSIS and PDAI almost perfectly. Besides, it was shown that the evaluation of patients' oral involvement based on PDAI and ODSS is done in about 1 min, which seems clinically reasonable.

The effect of autoimmune skin disorders on post-operative outcomes following arthroplasty.

INTRODUCTION: The impact of autoimmune skin disorders on post-operative outcomes after TJA is conflicting and studies are limited by small sample sizes. The purpose of this study is to analyze a range of common autoimmune skin disorders and identify whether an increased risk of post-operative complication exists after total joint arthroplasty. METHODS: Data was collected from NIS database for patients diagnosed with autoimmune skin disorder (psoriasis, lupus, scleroderma, atopic dermatitis) and who underwent total hip arthroplasty (THA), total knee arthroplasty (TKA), or other TJA (shoulder elbow, wrist, ankle) between 2016 and 2019. Demographic, social, and comorbidity data was collected. Multivariate regression analyses were performed to assess the independent influence of autoimmune skin disorder on each post-operative outcome including implant infection, transfusion, revision, length of stay, cost, and mortality. RESULTS: Among 55,755 patients with autoimmune skin disease who underwent TJA, psoriasis was associated with increased risk of periprosthetic joint infection following THA (odds ratio 2.44 [1.89-3.15]) and increased risk of transfusion following TKA (odds ratio 1.33 [1.076-1.64]). Similar analyses were performed for systemic lupus erythematosus, atopic dermatitis, and scleroderma, however no statistically significant associations were observed in any of the six collected post-operative outcomes. CONCLUSION: This study suggests psoriasis is an independent risk factor for poorer post-operative outcomes following total joint arthroplasty, however similar risk was not observed for other autoimmune skin disorders such as lupus, atopic dermatitis, or scleroderma.

Olmsted syndrome causing point mutants of TRPV3 (G568C and G568D) show defects in intracellular Ca2+-mobilization and induce lysosomal defects.

TRPV3, a non-selective cation channel known to be activated by physiological temperature, is expressed in skin and is involved in different skin functions. Point mutations in TRPV3 cause severe pathological condition, known as Olmsted Syndrome (OS). Now we demonstrate that two OS-inducing point mutations (G568C and G568D) located at the lipid-water-interface region joining TM4 with the loop4 of TRPV3 cause reduced cell size and major defects in lysosomal numbers, and distribution. We detected these two mutants in the lysosome. However, G568C and G568D mutants differ from themselves and also from Wild-type in terms of Ca2+-influx in response to activation by agonist (FPP). These two mutants fail to mobilise Ca2+ from intracellular stores, especially when cytosolic Ca2+ is chelated and/or in absence of extracellular Ca2+. We demonstrate that OS-mutants cause defective pH-maintenance at the lysosomes. We propose that G568C and G568D mutants most-likely act as Ca2+-leaky channels from lysosomes with different abilities.

Genetic skin disorders: The value of a multidisciplinary clinic.

Genodermatoses are inherited disorders with skin manifestations and can present with multisystem involvement, resulting in challenges in diagnosis and treatment. To address this, the expertise of dermatology and clinical genetics through a multidisciplinary clinic (Genodermatoses Clinic) were combined. A retrospective cohort study of 45 children seen between March 2018 and February 2019 in the Genodermatoses Clinic at The Children's Hospital of Philadelphia was performed. Patient demographics, referral information, genetic testing modality, diagnoses, and patient satisfaction scores were evaluated to assess the clinic's impact. The majority of patients (42.2%) were referred from Dermatology and 86.7% were referred for diagnosis. Two-thirds of the patients were recommended genetic testing, and subsequently 73.3% completed testing. Nearly three-quarters, 26 out of 36 patients (72.2%), of our undiagnosed patients received a clinical and/or molecular diagnosis, which is imperative in managing their care. Twenty-two individuals pursued genetic testing. In eight individuals (36%), molecular testing was diagnostic. However, in two individuals the molecular diagnosis did not completely explain the phenotype. However, there are still obstacles to genetic testing, such as cost of testing and insurance barriers. Almost all (91.4%) rated the Genodermatoses Clinic as "Very Good," the top Press Ganey score. High patient satisfaction scores suggest a positive impact of the Genodermatoses clinic, emphasizing the importance to increase support for the clinical and administrative time needed for patients with genodermatoses.

Nanodelivery Systems for Topical Management of Skin Disorders.

Topical drug delivery has inherent advantages over other administration routes. However, the existence of stratum corneum limits the diffusion to small and lipophilic drugs. Fortunately, the advancement of nanotechnology brings along opportunities to address this challenge. Taking the unique features in size and surface chemistry, nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, and framework nucleic acids have been used to bring drugs across the skin barrier to epidermis and dermis layers. This article reviews the development of these formulations and focuses on their applications in the treatment of skin disorders such as acne, skin inflammation, skin infection, and wound healing. Existing hurdles and further developments are also discussed.

The Influence of Intervening on the Pharmaceutical Consultation Targeting Outpatients with Advanced Non-small Cell Lung Cancer Receiving Erlotinib Treatment.

Erlotinib is used to treat advanced non-small-cell lung cancer (NSCLC), the common serious adverse events are skin disorders. The dose intensity of erlotinib should be maintained as much as possible by an appropriate control of adverse events in order to maintain its efficacy. Therefore, the management of these adverse events related to skin disorders would enable a continuous erlotinib treatment without interruption and dose reduction. This study assessed the effect of pharmaceutical consultation in outpatients who received erlotinib. Participants included patients with NSCLC who received erlotinib therapy for more than 6 months between December 2007 and March 2019. The participants were divided into two groups: the intervention group that included patients who received pharmaceutical consultation targeting outpatients by a pharmacist and the nonintervention group that included patients who did not. We retrospectively investigated patient characteristics, treatment regimens, and treatment efficacy. We included a total of 33 patients (18 and 15 patients in the nonintervention and intervention groups, respectively) in this study. The intervention group had a significantly higher median relative dose intensity (RDI) of erlotinib than the nonintervention group (p = 0.0437). In addition, the pharmaceutical consultation targeting outpatients was identified as a factor contributing to the maintenance of RDI ≥90% (p = 0.0269). The present study indicated that there was improvement in RDI with pharmaceutical consultation targeting outpatients with advanced NSCLC.

Analysis of risk factors for skin disorders caused by anti-epidermal growth factor receptor antibody drugs and examination of methods for their avoidance.

WHAT IS KNOWN AND OBJECTIVE: Cancer drug treatment is often discontinued because of skin disorder aggravation. However, information on risk factors for skin disorders caused by anti-epidermal growth factor receptor (EGFR) antibody drugs is limited. The aim of this study was to analyse the factors associated with skin disorders caused by anti-EGFR antibody drugs and establish a method to minimize such aggravations. METHODS: We retrospectively examined 67 colorectal cancer patients treated with anti-EGFR antibody drugs for the first time. RESULTS AND DISCUSSION: A higher proportion of males than females experienced drug withdrawal, dose reduction or treatment discontinuation. The multiple logistic regression analysis revealed body weight as a risk factor affecting drug withdrawal, dose reduction or treatment discontinuation because of an acneiform rash. An examination of methods to avoid the aggravation of skin disorders revealed the acneiform rash grade in patients who received prophylactic minocycline was significantly lower than that in patients who did not receive prophylactic minocycline. Furthermore, among patients with grade 1 acneiform rash at the initiation of minocycline, the proportion of those who withdrew, required dose reduction or discontinued treatment was lower than that among patients with grade 2 acneiform rash. WHAT IS NEW AND CONCLUSION: High body weight was identified as a novel factor for skin disorder aggravation caused by anti-EGFR antibody drugs. The aggravation of skin disorders during cancer treatment with anti-EGFR antibody drugs can potentially be avoided by carefully observing the onset of acneiform rash in affected patients with high body weight and using minocycline prophylactically or as an early-stage intervention.

Potential herbal constituents for psoriasis treatment as protective and effective therapy.

Psoriasis is a multifactorial and chronic skin disorder. It is a recurrent disease that requires incessant therapy. Psoriasis treatment includes topical and systemic routes using synthetic drugs that lead to severe unwanted adverse effects. Herbal therapy is widely used for thousands of years in countries like China and India. The use of herbal therapy in the developed region enhanced to a great extent and showed better efficacy towards psoriasis alone or as adjuvant to synthetic therapy. Herbal medicines have gained great attention in the treatment of psoriasis due to their lesser side effects compared to synthetic drugs. In this review, the various plant sources which have been found effective in psoriasis and can be used to develop novel therapeutics have been discussed. The mechanisms by which the phytoconstituents elicit anti-psoriatic activity and various research studies that have proven the effectiveness of these natural products have also been compiled in this review.

A systematic review on efficacy, safety, and treatment-durability of low-dose rituximab for the treatment of Pemphigus: special focus on COVID-19 pandemic concerns.

BACKGROUND: Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on assessments of efficacy and safety of low-dose rituximab (<2 gram in each cycle). METHOD: Databases were searched from 2010 to 2020 (last update: 1 June 2020). RESULT: Nine studies were entered; including180 cases (92: women, 88: men, age range: 9-83 years). The dosages of each Rituximab cycle varied between ultra-low-dose (≤500 mg for a cycle, either multiple infusions or a single infusion), low-dose (2 × 375 mg/m2 or 2 × 500 mg) and modified-dose (3 × 375 mg/m2 or 3 × 500 mg). The efficacy and safety of Rituximab in the studies are known by the recovery time, relapse time, and side events. According to the studies, 2 × 500 can lead to complete remission in a broad range, from 35 to 82%. These differences might be explained by different end-points and variable cumulative corticosteroid dosage after RTX administration. Although the studies showed that low dose RTX is efficient, there are some controversies regarding the choosing low-dose for severe patients. CONCLUSION: Considering the effectiveness of low-dose, intermediate dose, and ultra-low-dose protocols of Rituximab in inducing remission in pemphigus disease and considering factors such as cost of therapy, and the need to induce a minimum of immunosuppression for a minimum duration in the COVID-19 pandemic, suggested to use low-dose Rituximab protocol (2 infusions of 500 mg Rituximab: interval of 2 weeks) to induce the remission in mild-to-moderate pemphigus patients.

A heterozygous mutation in GJB2 (Cx26F142L) associated with deafness and recurrent skin rashes results in connexin assembly deficiencies.

Mutations in GJB2 encoding Connexin 26 (CX26) are associated with hearing loss and hyperproliferative skin disorders of differing severity including keratitis-ichthyosis-deafness (KID) and Vohwinkel syndrome. A 6-year-old Caucasian girl who presented with recurrent skin rashes and sensorineural hearing loss harboured a heterozygous point mutation in GJB2 (c.424T > C; p.F142L). To characterize the impact of CX26F142L on cellular events. Plasmids CX26WT, CX26F142L, CX26G12R (KID) or CX26D66H (Vohwinkel) were transfected into HeLa cells expressing Cx26 or Cx43 or into HaCaT cells, a model keratinocyte cell line. Confocal microscopy determined protein localization. MTT assays assessed cell viability in the presence or absence of carbenoxolone, a connexin-channel blocker. Co-immunoprecipitation/Western blot analysis determined Cx43:Cx26 interactions. Quantitative real-time polymerase chain reaction assessed changes in gene expression of ER stress markers. Dye uptake assays determined Connexin-channel functionality. F142L and G12R were restricted to perinuclear areas. Collapse of the microtubule network, rescued by co-treatment with paclitaxel, occurred. ER stress was not involved. Cell viability was reduced in cells expressing F142L and G12R but not D66H. Unlike G12R that forms "leaky" hemichannels, F142L had restricted permeability. Cell viability of F142L and G12R transfected cells was greater in HeLa cells expressing Cx43 than in native Cx-free HeLa cells. Co-immunoprecipitation suggested a possible interaction between Cx43 and the three mutations. Expression of CX26F142L and G12R results in microtubule collapse, rescued by interaction with Cx43. The GJB2 mutations interacted with Cx43 suggesting that unique Cx43:Cx26 channels are central to the diverse phenotype of CX26 skin-related channelopathies.

Minocycline prevents and repairs the skin disorder associated with afatinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors for non-small cell lung cancer.

BACKGROUND: While epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) exert a breakthrough effect, the incidence of skin disorders as a side effect has significantly reduced patients' quality of life. This study aimed to develop a treatment for inflammatory ulcers as one of the side effects of afatinib (Giotrif®), a second-generation EGFR-TKI, and established a skin disorder mouse model to investigate the protective effect of minocycline. METHODS: First, under inhalation anesthesia with isoflurane, the back of a male ddy mouse was shaved, and afatinib petrolatum was applied alone or in combination with minocycline to observe the state of the skin and measure transepidermal water transpiration (TEWL). Next, afatinib was administered orally to mice, and minocycline petrolatum was applied to observe whether the skin disorder was prevented and its effect on repair of the skin disorder. RESULTS: Skin injury occurred on the back of the mouse following afatinib (1 mg/g in petrolatum) application, and scab formation was observed. Application of minocycline prevented and improved the skin disorder caused by afatinib. When the minocycline-petrolatum mixture was applied to the mouse that developed the skin disorder, a significant improvement in TEWL was observed, and skin repair was observed macroscopically. CONCLUSIONS: These results suggest that minocycline petrolatum applied locally prevents and repairs afatinib-induced skin disorders of non-small cell lung cancer patients. Histological examination of skin has provided insights into the mechanism of the occurrence of afatinib-related skin disorder and suggested the efficacy of minocycline topical application in clinical practice.

An IL17RA frameshift variant in a Holstein cattle family with psoriasis-like skin alterations and immunodeficiency.

BACKGROUND: Skin lesions and dermatoses in cattle are often associated with infections due to bacteria, fungi or environmental risk factors. Dermatoses with genetic etiology have been described in cattle. Among these rare disorders, there are primary congenital dermatoses that are associated with inherited nutritional deficiencies, such as bovine hereditary zinc deficiency or zinc deficiency-like syndrome. This study presents three cases of Holstein cattle with congenital skin lesions observed on a single farm that resemble zinc deficiency-like syndrome. Close clinical and pathological examinations took place in two cases. Pedigree analysis indicated autosomal recessive inheritance and whole-genome sequencing of both affected calves was performed. RESULTS: The two calves showed retarded growth and suffered from severe ulcerative dermatitis with hyperkeratosis, alopecia furunculosis and subcutaneous abscess formation. Blood analysis showed correspondent leukocytosis with neutrophilia whereas minerals, macro- and micronutrients were within the reference ranges. Variant calling and filtering against the 1000 Bull Genomes variant catalogue resulted in the detection of a single homozygous protein-changing variant exclusively present in both sequenced genomes. This single-nucleotide deletion in exon 3 of IL17RA on bovine chromosome 5 was predicted to have a deleterious impact on the encoded protein due to a frameshift leading to a truncated gene product. Genotyping of the affected cattle family confirmed recessive inheritance. CONCLUSIONS: A loss-of-function mutation of the IL17RA transmembrane protein could be identified as most likely pathogenic variant for the psoriasis-like skin alterations observed in the two affected Holstein calves. In man, rare recessive diseases associated with IL17RA include immunodeficiency 51 and chronic mucocutaneous candidiasis. This supports the observed immunodeficiency of the presented cases. This study reports the first naturally occurring IL17RA-associated animal model.

Estimated cut-off values for pemphigus severity classification according to pemphigus disease area index (PDAI), autoimmune bullous skin disorder intensity score (ABSIS), and anti-desmoglein 1 autoantibodies.

BACKGROUND: Pemphigus is a potentially fatal disease if left untreated. Valid scoring systems and defined cut-off values for classification of patients would help with better management through specified pharmaceutical and non-pharmaceutical treatments. METHODS: In this study, pemphigus patients who were receiving immunosuppressive treatments and had recent disease relapse were recruited for examination of pemphigus disease area index(PDAI), autoimmune bullous skin disorder intensity score (ABSIS), physician global assessment (PGA), autoimmune bullous disease quality of life (ABQoL), anti-desmoglein 1 (anti-Dsg1), and anti-Dsg3 autoantibody titers from December-2017 to February-2018. Cut-off values were estimated using model-based clustering classification and the 25th and 75th percentiles approach, performed separately for the exclusive cutaneous, exclusive mucosal, and mucocutaneous groups. RESULTS: In the 109 included patients, the 25th and 75th percentiles cut-offs were 6.2 and 27 for PDAI score, and 4 and 29.5 for ABSIS score. The model-based analysis resulted in two groups (cut-point:15) for PDAI score, and three groups (cut-points:6.4 and 31.5) for ABSIS score. The groups were significantly different for the PDAI, ABSIS, PGA, and ABQoL values. Based on anti-Dsg1 autoantibody values, the model-based analysis cut-point was 128 and the 25th and 75th percentiles cut-offs were 98 and 182. Anti-Dsg3 autoantibody values did not differentiate between pemphigus severity classes. CONCLUSIONS: Estimated cut-off values based on the anti-Dsg1 level, PDAI, and ABSIS scoring systems could be used to classify patients into different severity grades for better management and prognosis.

Pleiotropic Role of Notch Signaling in Human Skin Diseases.

Notch signaling orchestrates the regulation of cell proliferation, differentiation, migration and apoptosis of epidermal cells by strictly interacting with other cellular pathways. Any disruption of Notch signaling, either due to direct mutations or to an aberrant regulation of genes involved in the signaling route, might lead to both hyper- or hypo-activation of Notch signaling molecules and of target genes, ultimately inducing the onset of skin diseases. The mechanisms through which Notch contributes to the pathogenesis of skin diseases are multiple and still not fully understood. So far, Notch signaling alterations have been reported for five human skin diseases, suggesting the involvement of Notch in their pathogenesis: Hidradenitis Suppurativa, Dowling Degos Disease, Adams-Oliver Syndrome, Psoriasis and Atopic Dermatitis. In this review, we aim at describing the role of Notch signaling in the skin, particularly focusing on the principal consequences associated with its alterations in these five human skin diseases, in order to reorganize the current knowledge and to identify potential cellular mechanisms in common between these pathologies.

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.

Exposure-based cognitive behavior therapy for atopic dermatitis: an open trial.

Atopic dermatitis (AD) is a common and debilitating inflammatory dermatological disorder and is marked by itch and inflamed skin. Scratching, sleep loss, and avoidance of situations associated with more AD symptoms are central hypothesized mechanisms that perpetuate the disorder and cause reduced quality of life. We developed an exposure-based cognitive behavioral treatment (CBT) that entailed mindfulness practice as a means to increase tolerance for aversive experiences during exposure. The aim of the present study was to test the treatment's acceptability and preliminary efficacy in adults with AD. We used an uncontrolled pretest-posttest design and recruited participants (N = 9) from a university hospital dermatological clinic. The treatment comprised 10 weekly sessions over 10 weeks and assessments of AD symptoms as well as psychiatric symptoms and quality of life were conducted at baseline, posttreatment and 6-month follow-up. The results showed significant and large baseline to posttreatment improvements on self-reported measures of AD symptoms (p = .020) and general anxiety (p = .005), but there was no significant improvement in depression or quality of life. Treatment satisfaction was high and a majority of participants (67%) completed the treatment. We conclude that exposure-based CBT for adult AD can be feasible, acceptable, and potentially efficacious.