Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.

Pruritus related to trastuzumab and pertuzumab in HER2 + breast cancer patients.

PURPOSE: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. METHODS: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. RESULTS: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. CONCLUSIONS: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Multi-center retrospective review of vitiligo-like lesions in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors.

PURPOSE: Cutaneous adverse effects from cyclin-dependent 4 and 6 kinase inhibitors (CDK4/6i) used in metastatic breast cancer are prevalent and well described. Vitiligo-like lesions have been reported and are rare. They can negatively impact patients' quality of life and may be associated with survival benefits. We describe the clinical characteristics of vitiligo-like lesions in an international cohort of patients treated with CDK4/6i to help improve recognition and management. METHODS: Retrospective review of patients diagnosed with vitiligo-like lesions from CDK4/6i from five academic institutions in the USA and Europe was performed. Ten patients were included in the study. RESULTS: Median age of our patients was 55 (range 37-86). Median progression-free survival was 24 months in 5 patients. The median time to rash was 10 months. Sun-exposed areas such as the arms and face were the most affected areas. Multiple skin-directed therapies such as topicals, laser, and phototherapy were trialed with minor success. Mild repigmentation was seen in one patient treated with ruxolitinib cream. CDK4/6 treatment was discontinued due to the vitiligo-like lesions in one patient. CONCLUSION: Clinical characteristics are similar to previously reported findings in case reports and series. We add topical ruxolitinib as a potential treatment option for these patients and include data regarding progression-free survival that should continue to be collected. No definitive conclusions can be made regarding survival benefits from our cohort. Clinicians should refer these patients to dermatologists to aid with management.

Expanding the phenotype of Harel-Yoon syndrome: A case report suggesting a genotype/phenotype correlation.

Harel-Yoon syndrome (HAYOS) is a unique neurodevelopmental genetic disorder characterized by hypotonia, spasticity, intellectual disability, hypertrophic cardiomyopathy, and global developmental delay. It primarily results from mutations in the ATAD3A gene, pivotal for mitochondrial function. This report presents a 5-year-old girl with HAYOS harboring a de novo heterozygous variant c.1064G>A; (p.G355D) in ATAD3A. Her clinical profile includes delayed milestones, hypotonia, spastic quadriplegia, and ptosis. Notably, dermatologic anomalies such as hypopigmentation, café au lait macules, and freckling are observed, expanding the known phenotype of HAYOS. The inclusion of dermatologic features challenges our understanding of the syndrome and emphasizes the importance of further research to elucidate the molecular connections between ATAD3A mutations and dermatologic manifestations.

Dermatologic manifestations of hematologic disorders.

Distinguishing key morphologic features and understanding the pathophysiology of common cutaneous manifestations of hematologic disorders is essential to ensure prompt and appropriate treatment. In fact, classic cutaneous signs may provide the first clue to the diagnosis of an underlying hematologic disease. Disorders of coagulation, vascular abnormalities, or cutaneous infiltration and deposition are responsible for the underlying pathophysiology of cutaneous manifestations in the majority of cases. Hematologists often feel ill-equipped in identifying morphologic changes in the skin. Thus, the purpose of this review is to provide a comprehensive overview of classic cutaneous manifestations and diagnostic considerations of the associated hematologic conditions. Though there is a specific focus on non-malignant disorders, those straddling the spectrum of malignancy are also discussed. In many disease states, the skin may serve as an important marker of an emerging hematologic disorder, so close collaboration and multidisciplinary input remain essential to provide optimal and timely care for these patients.

Activity Limitation Counseling in Dermatologic Surgery: A Survey and Retrospective Chart Review.

INTRODUCTION: Perioperative counseling regarding activity limitations is critical for patients undergoing dermatologic surgery. Current postoperative instructions regarding activity limitations may be inadequate, but this cannot be determined without knowing patient expectations. The study objective was to elucidate patient expectations for counseling on postoperative activity limitations and to determine if increased counseling would impact patient planning pre or postoperatively. MATERIALS AND METHODS: Patients who had excisions on the neck, torso, or extremities at one institution in one calendar year by the same surgeon participated in a phone survey. Questions addressed preexisting activity level, activity changes after surgery, amount of counseling received, and perioperative counseling expectations. Multivariable logistic regression was used to determine factors associated with patient perceptions about counseling, activity limitations, and surgical outcomes. RESULTS: Patients counseled on postoperative activity limitations reported they were unlikely to have made further arrangements to their surgical/personavl schedule had they been given additional counseling. The inverse was also true. When patients received the amount of counseling they expected, they were less likely to want to reschedule surgery or adjust personal plans. Younger patients and those with surgery on the lower extremities were more likely to limit their activity for longer periods of time. CONCLUSIONS: As instructions on activity limitations become more transparent, patients can make informed decisions regarding their surgical and personal schedules. This study can guide dermatologic surgeons in adjusting postoperative instructions to improve patient understanding of activity limitations, compliance, and the overall quality of their surgical experience.

Dermatologic toxicities of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a new and emerging category of oncologic treatments that combine the target specificity of a monoclonal antibody with a cytotoxic payload. These drugs are associated with unique cutaneous toxicities that vary across agents. Currently, there are eleven ADCs with regulatory approval for solid and liquid tumors and over 80 ADCs currently in clinical development, it is critical for dermatologists to recognize and appropriately mitigate the cutaneous toxicities associated with these therapies. This clinical review will summarize the novel mechanisms and indications of approved ADCs, discuss dermatologic toxicities demonstrated in clinical trials and postmarketing studies, and impart recognition and management guidance when encountering these reactions to help maintain patients safely and comfortably on their medications.

Excision margins for melanoma in situ on the head and neck-A single-center 10-year retrospective review of treatment with Mohs micrographic surgery.

BACKGROUND: Although current guidelines recommend a 5 mm surgical margin for the excision of melanoma in situ (MIS), increasing evidence has shown this may be suboptimal to achieve tumor clearance. OBJECTIVE: To evaluate margins required for optimal cure rates with excision of MIS on the head and neck and investigate tumor and/or patient factors in those requiring >5 mm margins to achieve tumor clearance. METHODS: A retrospective chart review was performed on 846 (807 primary and 39 recurrent) MIS cases on the head and neck treated in the authors' dermatologic surgery department over a 126-month (10.5 year) period. RESULTS: Sixty-two percent were cleared with 5 mm margins. A total of 15 mm margins were required to achieve a 97% clearance rate. Difference in clearance rate between margin thresholds was significant (P < .001). Tumor location on the cheek and larger preoperative size correlated with requiring >5 mm margins to achieve tumor clearance (P = .006 and P = .001, respectively). LIMITATIONS: This is a single-center retrospective study which relies on accurate documentation of clinical data. CONCLUSION: This study demonstrates that MIS on the head and neck often requires margins >5 mm margins to achieve tumor clearance. When Mohs micrographic surgery is not possible, excision margins of ≥10 mm are likely necessary for head and neck tumors.

Early postoperative water exposure does not increase complications in cutaneous surgeries: A randomized, investigator-blinded, controlled trial.

BACKGROUND: Patients are often advised to keep the initial postoperative dressings dry and undisturbed for 24 to 72 hours. However, these requirements may result in significant disruption of patients' activities of daily living, such as bathing, leisure, and exercise. OBJECTIVE: Compare standard management of keeping wounds dry and covered (48 hours) with early (6 hours) postoperative water exposure. METHODS: Investigator-blinded, randomized (1:1), controlled trial evaluating rate of infection and additional outcomes of interest. RESULTS: Overall, 437 patients were randomized to either the early (6-hour) water exposure (n = 218) intervention group or the standard cohort (n = 219). The incidence of culture-proven infection in the intervention group (1.8%) was similar to the standard group (1.4%) (P > .99). There was also no difference in rates of bleeding or bruising. Scar assessment using the Patient and Observer Scar Assessment Scale revealed similar scar outcomes. LIMITATIONS: Single site, academic center. CONCLUSION: Surgical wounds can be allowed to get wet in the immediate postoperative period with no increased incidence of infection or other complications and with similar cosmesis.

Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown. PURPOSE: We assessed if delays in ttPORT were associated with inferior outcomes. METHODS: Competing risk regression was used to evaluate associations between ttPORT and locoregional recurrence (LRR) for patients with stage I/II MCC in a prospective registry and adjust for covariates. Distant metastasis and death were competing risks. RESULTS: The cohort included 124 patients with median ttPORT of 41 days (range: 8-125 days). Median follow-up was 55 months. 17 (14%) patients experienced a LRR, 14 (82%) of which arose outside the radiation field. LRR at 5 years was increased for ttPORT >8 weeks vs ≤ 8 weeks, 28.0% vs 9.2%, P = .006. There was an increase in the cumulative incidence of MCC-specific death with increasing ttPORT (HR = 1.14 per 1-week increase, P = .016). LIMITATIONS: The relatively low number of LRRs limited the extent of our multivariable analyses. CONCLUSIONS: Delay of PORT was associated with increased LRR, usually beyond the radiation field. This is consistent with the tendency of MCC to spread quickly via lymphatics. Initiation of PORT within 8 weeks was associated with improved locoregional control and MCC-specific survival.

Factors associated with residual tumor at time of Mohs micrographic surgery for basal cell and squamous cell carcinomas.

BACKGROUND: Residual tumor is not always clinically apparent following biopsy of cutaneous carcinomas, which may prompt patients to question the need for definitive treatment. OBJECTIVE: We investigated the percentage of cases in which residual tumor was histologically present at the time of Mohs micrographic surgery (MMS) for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) and investigated factors associated with residual tumor. METHODS: We examined 483 MMS cases performed for biopsy-proven BCC (n = 287) and SCC (n = 196) between October 2022 and April 2023. Single-stage MMS specimens were step-sectioned en face to exhaust the block. Univariate and multivariable logistic regression models were created. RESULTS: Residual tumor was identified in 83.3% of BCC and 66.8% of SCC at the time of MMS (P = .01). In patients clinically appearing tumor-free following biopsy, residual histologic tumor was identified in 68.2% of BCC and 41.5% of SCC. Residual tumor was significantly more likely in men (P = .04), high-risk sites (P = .002), smaller biopsy sizes (P = .0003), and larger preoperative sizes (P < .0001). LIMITATIONS: Single center, retrospective cohort. CONCLUSION: The majority of patients with BCC and SCC have residual histologic tumor at the time of MMS, oftentimes even when tumor is not clinically apparent. Multiple factors impact the presence/absence of residual tumor.

Safety of dermatologic medications in pregnancy and lactation: An update-Part II: Lactation.

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation.

Ultrasound Pattern of Cutis Verticis Gyrata.

Cutis verticis gyrata (CVG) is a cutaneous benign condition that usually presents symmetric or asymmetric convoluted folds and deep furrows in the scalp, which mimic the disposition of the cerebral sulci and gyri. This scalp deformation may be a worrying situation for the patients and their families. Clinically, its diagnosis may be challenging because it can mimic other cutaneous conditions. So far, the ultrasonographic pattern of CVG has not been reported. Thus, we aim to review the ultrasound findings of this entity. All patients (n = 14) presented zones with dermal and hypodermal thickening that corresponded with the elevated clinical zones, followed by folds with normal cutaneous thicknesses. There was undulation of the cutaneous layers in all cases. The scalp areas involved the frontal, parietal, and occipital regions bilaterally. The mean maximum dermal and hypodermal thicknesses and echogenicities and the color Doppler characteristics are provided. No significant dilation of the hair follicles was detected. In conclusion, CVG presents an ultrasonographic pattern that can support its diagnosis and follow-up. This can help its differential diagnosis with other scalp dermatologic conditions.

Ultrasound Patterns of Vitiligo at High Frequency and Ultra-High Frequency.

OBJECTIVES: To detect ultrasonographic anatomical alterations in all the skin layers in patients with vitiligo. METHODS: A prospective observational color Doppler ultrasound study was performed in nonsegmental face and/or neck vitiligo patients without a history of previous treatments. Two sites, a lesional area and a contralateral clinically healthy region, were ultrasonographically studied and compared in the same patient. All cases were studied in high-frequency (24 MHz) and ultra-high-frequency (70 MHz) ultrasound devices with the highest axial spatial resolution available in the market. Demographic data of the sample, ultrasound grayscale, and color Doppler features were recorded and analyzed. RESULTS: Ten patients met the study criteria (60% females; mean age 49 years). All cases presented ultrasonographic undulation of the epidermis in the affected zones vs 50% in the healthy control regions, being more prominent in the vitiligo areas. Eighty percent demonstrated intense hypoechoic thin plaques in the upper dermis (subepidermal). All vitiligo areas presented thickening and hypoechogenicity of the regional hair follicles and/or pilosebaceous units. Ninety percent showed prominent sebaceous glands, and 20% demonstrated a hypoechoic cap surrounding the sebaceous glands in the lesional areas. Dermal hypervascularity was detected in 100% of the affected regions and 40% of the clinically healthy areas. CONCLUSION: Ultrasound can identify subclinical inflammatory cutaneous patterns in the epidermis, dermis, hair follicles, pilosebaceous units, and sebaceous glands in vitiligo. This noninvasive information can support early detection, monitoring, and research, including the clinical trials of drugs used to manage this devastating disease.

Ultrasound Features of Nail Lichen Planus.

OBJECTIVES: To describe the ultrasonographic features of nail lichen planus (NLP), which, so far, have not been reported in the literature. METHODS: A retrospective single-center study of NLP patients' color Doppler ultrasound examinations was performed between March 2014 and January 2023. Inclusion criteria were patients ≥15 years with a confirmed clinical diagnosis of NLP in sequential order. Exclusion criteria included concomitant systemic or local cutaneous or nail diseases and systemic or local nail treatments before the ultrasound examination. The ultrasound protocol included the examination of all fingernails or toenails following the reported protocol for dermatologic ultrasound examinations at high and ultra-high frequencies. Patient demographics and ultrasound features of the nail bed, periungual region, nail plate, and regional vascularity were registered and analyzed statistically. RESULTS: A total of 36 patients met the criteria. All cases presented thickened and decreased echogenicity of the nail bed. A hypoechoic halo surrounding the origin of the nail plate was present in 78% of cases. Exactly 58% of patients presented decreased echogenicity of the proximal periungual dermis, and 86% showed thickening of the periungual dermis. Hypervascularity of the nail bed was seen in 94% of cases. The mean maximum thickness of vessels, the peak systolic velocity of the arterial vessels, and other blood flow findings are provided. CONCLUSION: Ultrasonography can support the diagnosis of NLP, which benefits the non-invasive discrimination of nail conditions and can avoid the potential permanent scars derived from nail biopsies. Furthermore, ultrasound may be a powerful tool to monitor this disease's treatment.

The Usefulness of Ultrasonography for Supporting the Differentiation, Diagnosis, and Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare histomorphological variants of a disease spectrum. After ruling out other tumor entities by immunohistochemistry, PDS can be differentiated from AFX by infiltration into the subcutis, while AFX remains confined to the dermis. The therapeutic approach is more aggressive in PDS as it can potentially metastasize. We assessed the usefulness of preoperative sonography in differentiating between the two tumor entities by identifying a potential subcutaneous infiltration. In our patients (n = 13), preoperative sonography identified and differentiated AFX and PDS with 100% accuracy and even changed the initial histological suspicion of AFX to PDS in 3 cases (23%), which was confirmed after tumor resection. Preoperative sonography of these tumors could strengthen the clinical diagnosis, avoid a delay in therapy initiation and improve patient counseling. While for AFX, micrographic-controlled surgery suffices, for PDS, resection with 2 cm safety margins and lymph node sonography to rule out lymphonodal involvement is necessary. Hence, ultrasonography can improve clinical practice by providing helpful information for dermatosurgeons, which cannot be obtained during clinical examination.

Update on Ultrasound Diagnostic Criteria and New Ultrasound Severity and Activity Scorings of Hidradenitis Suppurativa: Modified SOS-HS and US-HSA.

Hidradenitis suppurativa (HS) is a devasting autoimmune cutaneous disease that affects the hair follicles and can clinically present palpable nodules, abscesses, and tunnels (fistulas), usually in the intertriginous regions. It has been widely reported that color Doppler ultrasound can detect subclinical abnormalities and stage the severity of the disease more accurately. Nevertheless, the ultrasound diagnostic criteria were reported with 15 MHz 10 years ago, and now it is possible to detect early anatomical abnormalities in HS using 70 MHz. Thus, an update of the ultrasonographic diagnostic criteria is needed. The most widely used sonographic staging of severity of HS (SOS-HS) includes the number of affected regions, besides counting the number of key lesions like pseudocysts, fluid collections, and tunnels; however, the total number of affected regions may fit better in an activity scoring. Furthermore, a high number of tunnels or communicated tunnels can complicate the management and may indicate an even more urgent treatment, which should be considered in the severity classification. To date, no hidradenitis scoring of activity has been reported in the literature, making it difficult to track the degree of inflammation under treatment objectively. Therefore, two new scorings are proposed. The first is an updated sonographic scoring of severity called modified SOS-HS (mSOS-HS), and the second is an activity ultrasound scoring of HS called US-HSA. Both staging systems can provide better anatomical information for discriminating the categories and, therefore, selecting more appropriate treatments and supporting research and clinical trials by giving more objective anatomical tools in real-world settings.

Ultrasonography of Facial and Submandibular Hidradenitis Suppurativa and Concomitance with Acne Vulgaris.

OBJECTIVES: To describe the ultrasound characteristics of facial and submandibular hidradenitis suppurativa (HS) and detect acne vulgaris (AV) concomitance in these cases. METHODS: We performed a retrospective study of the ultrasound images of patients with facial HS who had been clinically evaluated by dermatologists. The reported ultrasound diagnostic criteria, severity (mSOS-HS), and activity (US-HAS) staging of HS were used to categorize the patients. The finding of fragments of hair tracts within the key lesions (dilated hair follicles, pseudocysts, fluid collections, and tunnels) was considered a pivotal sign to discriminate HS from AV. Demographic and morphological analysis of the images were considered. RESULTS: Thirty-three patients met the criteria (78.8% male/21.2% female). Of these, the mSOS- HS scoring was stage I in 51.5%, stage II in 27.3%, and stage III in 21.2%. Dilation of the hair follicles and the presence of pseudocysts, fluid collections, and tunnels were detected in the HS cases; 63.1% of pseudocysts, 62.4% of tunnels, and 46.2% of fluid collections contained fragments of hair tracts. In all HS cases, there was a key lesion(s) with fragments of hair tracts. Four (12.1%) patients showed concomitant facial HS and acne ultrasound lesions. The acne lesions were pseudocysts without inner hair tract fragments in all cases, and the SOS-Acne scoring was stage II for all of them. CONCLUSION: Facial HS can be detected on ultrasound and shows a morphology similar to that of HS in other corporal regions. In some cases, facial HS could be concomitant with AV. The subclinical ultrasonographic information can support a better management of these cases.

Dupilumab-induced psoriasiform dermatitis in two pediatric cardiac transplant patients.

Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.

Dermatological considerations for transgender and gender diverse patients: An Australian perspective.

Transgender and gender diverse (TGD) individuals are a group that experiences significant health disparities. In the multidisciplinary management of TGD patients, dermatologists may participate in managing skin- and hair-related issues which contribute to gender affirmation and to the cutaneous sequelae of gender-affirming hormone therapy. This review aims to highlight the unique needs of TGD patients, particularly from the perspective of Australian dermatologists. We review appropriate terminology critical for TGD care, gender affirmation in the Australian healthcare landscape, dermatological considerations for TGD patients and considerations for management.