Psychiatric disorders and suicidal behavior in patients with acne prescribed oral antibiotics versus isotretinoin: Analysis of a large commercial insurance claims database.

BACKGROUND: The association between isotretinoin and psychiatric disturbance, including depression and suicidal behavior, is controversial. OBJECTIVE: To investigate whether acne patients prescribed isotretinoin or antibiotics were more likely to have psychiatric disorders and/or engage in suicidal behavior. METHODS: Retrospective cohort study using the IBM MarketScan Research Databases, which contain commercial insurance claims in the United States, to identify acne patients who were prescribed isotretinoin or oral antibiotics between 2011 and 2017 and who were diagnosed with psychiatric disorders or suicidal behavior. RESULTS: A total of 72,555 patients were included in the study. Patients in the general population were 1.47 times more likely to be diagnosed with suicidal ideation or attempt compared to acne patients prescribed isotretinoin (adjusted odds ratio [OR] 1.47; confidence interval [95% CI], 1.27, 1.70; P < .0001). The general population (adjusted OR 0.87; 95% CI, 0.84, 0.89; P < .0001) and acne patients prescribed antibiotics (adjusted OR 0.88; 95% CI, 0.85, 0.91; P < .0001) were less likely to have a psychiatric diagnosis compared to acne patients prescribed isotretinoin. The prevalence of suicidal behavior during isotretinoin treatment was lower (0.10%; P = .082) than in the year prior to isotretinoin treatment (0.22%) and in the year following treatment (0.34%; P = .004). LIMITATIONS: The study excluded individuals with public insurance and those who were uninsured, and the data in the study relied on the accuracy of the medical coding. CONCLUSIONS: Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior. Further exploration into the slight increase in suicidal behavior seen in isotretinoin patients 1 year after therapy is warranted.

The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata.

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

Topical corticosteroid use for atopic dermatitis in the pediatric emergency department.

BACKGROUND/OBJECTIVES: To investigate the evaluation and management of atopic dermatitis (AD) in the pediatric emergency department (PED). METHODS: This retrospective chart review was performed at the PED of a single institution and examined data from 2012 to 2017. Of 335 visits from patients 18 years and younger coded for AD, 167 visits with documented findings that supported a diagnosis of AD according to guidelines from the American Academy of Dermatology were included. RESULTS: The mean age of presentation was 6.3 years (standard deviation [SD]: 5.9). Of 11 patients with multiple visits, the mean between-visit interval was 31 days (SD: 41). Topical corticosteroids (TCSs) were not prescribed or recommended in 63/167 visits. In an additional 46/167 visits, over-the-counter topical hydrocortisone was recommended. Of prescribed TCS, the mean TCS class was 5.5 (SD: 1.9). 61/104 recommended or prescribed TCSs were weak (Class 7), the most likely used class (P < .001). Dermatology consultation was requested in 14/167 visits and was associated with higher rates of TCS prescriptions (13/14 vs 91/153, P = .018), a higher mean class of TCS prescribed (3.1 vs 5.9, P < .001), higher prescription rates of systemic antibiotics (8/14 vs 10/153, P < .001), and higher recommendation rates for emollient usage (10/14 vs 46/153, P = .005). CONCLUSIONS: Most patients presenting to the PED for AD were either not prescribed a TCS or were prescribed a weak TCS, often one that is over-the-counter. While there may be a variety of explanations for these findings, it is possible they reveal a practice gap regarding AD management in the PED.

The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules.

BACKGROUND/OBJECTIVE: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.

The Alopecia Areata Consensus of Experts (ACE) study: Results of an international expert opinion on treatments for alopecia areata.

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.

A Review of Vitamin D and Scarring: The Potential for New Therapeutics.

Introduction: Recent research on vitamin D has shown that the fat-soluble micronutrient has anti-microbial, anti-inflammatory, and anti-proliferative effects in cells and tissues. During wound healing, abnormal scarring may occur and lead to reduced mobility, disfigurement, and psychosocial concerns. The role of vitamin D in the pathogenesis and treatment of scarring has not been reviewed previously. Methods: A literature search was performed on PubMed to identify articles on vitamin D and keloid, hypertrophic, or burn scars. Results: Molecular, epidemiological, and human clinical studies are discussed. Overall, the evidence suggests lower levels of vitamin D precursors, the active metabolite, and receptor, are associated with increased risk of scar development and increased severity. Conclusions: Scars are challenging to treat, and patients are increasingly interested in non-invasive treatment options. Although few human clinical studies have been reported, vitamin D may be beneficial as an adjunct therapy to current treatment options. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.4986.

Acquired acrodermatitis enteropathica due to zinc-depleted parenteral nutrition.

Well-known causes of zinc deficiency, also referred to as acrodermatitis enteropathica (AE), include defects in intestinal zinc transporters and inadequate intake, but a rare cause of acquired zinc deficiency discussed here is an iatrogenic nutritional deficiency caused by parenteral nutrition administered without trace elements. While zinc-depleted parenteral nutrition causing dermatosis of acquired zinc deficiency was first reported in the 1990s, it is now again relevant due to a national vitamin and trace element shortage. A high index of suspicion may be necessary to diagnose zinc deficiency, particularly because early clinical findings are nonspecific. We present this case of acquired zinc deficiency in a patient admitted to a pediatric intensive care unit for respiratory distress and atypical pneumonia, who subsequently developed a severe bullous eruption due to iatrogenic zinc deficiency but was treated effectively with enteral and parenteral zinc supplementation, allowing for rapid re-epithelialization of previously denuded skin.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest.

Characterization of Herpes Simplex Virus Infections Seen in the Pediatric Dermatology Office.

BACKGROUND/OBJECTIVES: Atypical and severe clinical manifestations of primary and recurrent herpes simplex virus (HSV) infections may present to a pediatric dermatologist for evaluation. The purpose of this study was to characterize the clinical features of the population diagnosed with HSV referred to a pediatric dermatology office. METHODS: This retrospective case series examined patients diagnosed with HSV in a pediatric dermatology practice at an academic medical center from 2005 to 2015. Characteristics of the population were collected and analyzed. RESULTS: In this study of 48 children diagnosed with HSV, 33% presented at age 2 years or younger, with approximately half having exhibited initial symptoms before 2 years of age; 39.6% of the population had six or more outbreaks per year. The outbreaks were equally divided between unifocal and multifocal presentations, with 60% of children without any labial or mucosal involvement. Suppressive treatment was initiated in 33% of patients; the average age at initiation was 6 years. CONCLUSION: Our data characterize a subset of immunocompetent young children who present to pediatric dermatologists with frequent HSV outbreaks that are often multifocal and involve cutaneous sites, with or without mucosal involvement.

Cole Disease Results from Mutations in ENPP1.

The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases.

The use of oral antibiotics before isotretinoin therapy in patients with acne.

BACKGROUND: Systemic antibiotics are used widely to treat moderate to severe acne, but increasing antibiotic resistance makes appropriate use a priority. OBJECTIVE: We sought to determine the duration of systemic antibiotic use in patients with inflammatory/nodulocystic acne who eventually required isotretinoin. METHODS: We performed a retrospective, single-site chart review of patients with acne diagnostic codes evaluated January 1, 2005 to December 31, 2014, at a dermatology practice in an academic medical center. Included patients were prescribed isotretinoin during the study period and received 30 days or more of antibiotics. RESULTS: The average duration of antibiotic use was 331.3 days. In all, 21 patients (15.3%) were prescribed antibiotics for 3 months or less, 88 patients (64.2%) for 6 months or more, and 46 patients (33.6%) for 1 year or longer. Patients treated only at the study site had a mean duration of antibiotic treatment of 283.1 days whereas patients who also received antibiotics from another institution had a mean duration of 380.2 days. This difference approached statistical significance (P = .054). LIMITATIONS: This study was limited to a single center. CONCLUSION: Expert guidelines recommend responsible use of antibiotics in acne in light of emerging resistance. We found that patients who eventually received isotretinoin had extended exposure to antibiotics, exceeding recommendations. Early recognition of antibiotic failure and the need for isotretinoin can curtail antibiotic use.

Segmental stiff skin syndrome (SSS): A distinct clinical entity.

BACKGROUND: Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. OBJECTIVE: We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. METHODS: This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. RESULTS: Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. LIMITATIONS: This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. CONCLUSIONS: We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features.

Cutaneous microbiome effects of fluticasone propionate cream and adjunctive bleach baths in childhood atopic dermatitis.

BACKGROUND: Patients with atopic dermatitis (AD) are prone to skin infections, with microbes such as Staphylococcus aureus suspected of contributing to pathogenesis. Bleach baths might improve AD by reducing skin microbial burden. OBJECTIVE: We sought to characterize the microbiota of lesional and nonlesional skin in young children with AD and control subjects and compare changes after treatment with a topical corticosteroid (TCS) alone or TCS + dilute bleach bath. METHODS: In a randomized, placebo-controlled, single-blinded clinical trial in 21 children with AD and 14 healthy children, lesional and nonlesional AD skin was examined at baseline and after 4-week treatment with TCS alone or TCS plus bleach bath. Microbial DNA was extracted for quantitative polymerase chain reaction of predominant genera and 16S rRNA sequencing. RESULTS: At baseline, densities of total bacteria and Staphylococcus, including Staphylococcus aureus, were significantly higher at the worst AD lesional site than nonlesional (P = .001) or control (P < .001) skin; bacterial communities on lesional and nonlesional AD skin significantly differed from each other (P = .04) and from control (P < .001). After TCS + bleach bath or TCS alone, bacterial compositions on lesional skin normalized (P < .0001), resembling nonlesional skin, with microbial diversity restored to control skin levels. LIMITATIONS: The 4-week time period and/or the twice-weekly baths may not have been sufficient for additional impact on the cutaneous microbiome. More detailed sequencing may allow better characterization of the distinguishing taxa with bleach bath treatment. CONCLUSIONS: Treatment with a TCS cream suffices to normalize the cutaneous microbiota on lesional AD; after treatment, bacterial communities on lesional skin resemble nonlesional skin but remain distinct from control.

Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi.

BACKGROUND: Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described. AIMS: We sought to provide an epidemiologic and clinical comparison of cases of childhood vitiligo presenting with or without associated halo nevi. MATERIALS AND METHODS: This was a retrospective chart review of children diagnosed with vitiligo in an academic pediatric dermatology practice from January 1990 to November 2014. The characteristics of children with vitiligo with or without associated halo nevi were compared. RESULTS: Halo nevi were identified in 55 (26%) of 208 children with vitiligo. Patients with halo nevi were significantly more likely to be male and develop vitiligo at a later age. Children with vitiligo associated with halo nevi were more likely to present with generalized vitiligo, defined according to the presence of bilateral macules. DISCUSSION: There was no significant association between groups in the percentage of body surface area with vitiligo or family history of vitiligo or autoimmune diseases. Patients with halo nevi were no more likely to develop new areas of vitiligo during the follow-up period, but there was a nonsignificant trend toward a higher rate of repigmentation in vitiligo associated with halo nevus. CONCLUSION: Halo nevi are a common finding in children with vitiligo. The presence of a halo nevus in a child with vitiligo is associated with generalized vitiligo. The presence of a halo nevus does not significantly alter the risk of disease progression and rate of treatment.

Early-onset childhood vitiligo is associated with a more extensive and progressive course.

OBJECTIVES: Vitiligo commonly presents in children, with half of all cases developing before 20 years of age. Although studies have characterized differences between pediatric and adult vitiligo, little is known about vitiligo presenting in early childhood. The purpose of this study was to compare clinical features of early-onset (<3 years old) and later-onset (3-18 years old) childhood vitiligo. METHODS: This retrospective case series examined patients given a diagnosis of vitiligo in a pediatric dermatology practice at an academic medical center from 1990 to 2014. Characteristics of the early- and later-onset groups were compared by χ(2) and t test for categorical and continuous variables, respectively. RESULTS: Of the 208 children in the study, 31 had early-onset and 177 had later-onset disease. Early-onset vitiligo was associated with higher percentages of body surface area involvement and increased rates of disease progression during an average 1.9 years of follow-up. There were no significant differences between the 2 groups in repigmentation, vitiligo type, halo nevi, gender ratio, or personal and family history of autoimmune diseases. LIMITATIONS: This was a retrospective, single-institution study. CONCLUSION: Patients given a diagnosis of vitiligo at younger ages tend to have more extensive and progressive disease.

Dermatologists' attitudes, prescription, and counseling patterns for isotretinoin: a questionnaire-based study.

Isotretinoin, the most effective therapy for severe acne, has engendered controversy. These controversies impact dermatologists' opinions of isotretinoin and prescription behaviors. This study was designed to characterize dermatologists' opinions of controversies surrounding isotretinoin, as well as counseling and prescribing practices. A 25-question survey was emailed to 7,013 dermatologists included in a proprietary database (MBD, Inc.) and anonymous responses were collected. 591 board-certified dermatologists participated. Thirty-seven percent of the responding dermatologists believe that isotretinoin may cause psychiatric disturbances. Dermatologists' opinions on this relationship did not significantly impact prescription practices in patients with history of depression (P=0.056) or in patients being treated with an antidepressant (P=0.118). A larger percentage of dermatologists surveyed believe there is a causal relationship between isotretinoin and psychiatric disturbances than isotretinoin and IBD. Of the surveyed dermatologists, 2.7% believe there is a causal association between isotretinoin and inflammatory bowel disease IBD. In addition, physicians with 20 or fewer years of experience, which included 50% of the responding dermatologists, were significantly less likely to have read the patient brochure (P=0.004), and more likely to prescribe isotretinoin to patients who had not failed systemic antibiotics (P=0.015). This questionnaire also may highlight a practice gap, as more recently trained dermatologists appear less likely to require failure of systemic antibiotics prior to initiating isotretinoin.

Genital melanocytic nevi in children: Experience in a pediatric dermatology practice.

BACKGROUND: Little is known about the prevalence and clinical characteristics of genital melanocytic nevi in children. OBJECTIVE: We sought to describe the epidemiology, clinical and dermoscopic features, and natural history of genital nevi in pediatric patients. METHODS: We reviewed charts of 1159 children given the diagnosis of melanocytic nevi over 11 years. Those with genital nevus as a chief symptom were contacted for follow-up. RESULTS: Among children/adolescents evaluated for nevi, the prevalence of genital nevus was 3.5% (40/1159), with a male:female ratio of 1.3:1. There were no statistically significant differences in age, sex, total nevus number, presence of acral and scalp nevi, or family history of dysplastic nevi and melanoma between patients with and without genital nevi. Genital nevus onset was before age 2 years in 63.6% of patients. A globular dermoscopic pattern was observed in 93.3%. Most genital nevi underwent a gradual change in diameter, elevation (becoming soft papules), color, texture, or a combination of these. After median follow-up of 1.5 years, no melanoma or other adverse outcome was observed. LIMITATIONS: This was a retrospective chart analysis and questionnaire-based study of a limited number of patients. CONCLUSIONS: Increased awareness of the clinical characteristics, dermoscopic features, and evolution of genital nevi in children may help to avoid unnecessary surgery.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts.

Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.