A case of mother and child with CANDLE syndrome: Diagnosis and subsequent treatment with baricitinib.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) or proteasome-associated autoinflammatory syndrome is a rare autoinflammatory disorder that typically presents in infancy with characteristic symptoms, including recurrent fever, panniculitis, and progressive lipodystrophy, among other findings. We present a case of mother and child with CANDLE syndrome. The child was eventually started on baricitinib with normalization of rash and systemic findings.

A Case Report of Primary Malignant Melanoma of the Gallbladder with Multiple Metastases.

Primary malignant melanoma of the gallbladder is an extremely rare tumor with approximately 39 cases described in the literature so far. However, since the first case was reported in 1907, it remains controversial whether gallbladder involvement in malignant melanoma is primary or metastatic. Here, we report a case of primary malignant melanoma of the gallbladder. A 52-year-old male presented to the emergency department with right upper quadrant abdominal pain and was found to have tumefactive sludge filling the majority of the gallbladder with possible gallbladder wall thickening on ultrasonography. A laparoscopic cholecystectomy was performed for presumed acute cholecystitis. Histopathologic examination of the gallbladder revealed malignant melanoma arising from the mucosa of the gallbladder. Further clinical investigation excluded other primary sites, supporting a diagnosis of primary malignant melanoma of the gallbladder.

Rosacea and Its Association With Malignancy: Systematic Review.

BACKGROUND: Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by the commonality of inflammatory and immune response dysfunction. Studies that have looked into this possible association have reported mixed results. OBJECTIVE: Given the conflicting literature on this topic, our study sought to evaluate the overall association between rosacea and several cancers commonly investigated in the literature. METHODS: A systematic review was conducted using the Cochrane, PubMed, Embase, and Ovid databases. Studies were screened independently for inclusion of rosacea and glioma and breast, thyroid, hepatic, or skin cancers. Using information from the articles, rosacea and each cancer were categorized as having a positive, negative, or unclear association. RESULTS: Our systematic review included 39 full-text studies that investigated the association between rosacea and various malignancies. Among the malignancies of concern, 41% (16/39) of the studies reported an association with basal cell carcinoma, with 2 cohorts revealing an adjusted risk ratio (RR) of 1.50 (95% CI 1.35-1.67) and 0.72 (95% CI 0.56-0.93). In total, 33% (13/39) of the studies reported an association with squamous cell carcinoma, with 2 cohorts revealing an adjusted RR of 1.4 (95% CI 1.02-1.93) and 1.30 (95% CI 0.90-1.88). A total of 8% (3/39) of the studies reported an association between breast cancer and melanoma, with breast cancer cohorts revealing an adjusted RR of 8.453 (95% CI 1.638-43.606), 1.03 (95% CI 0.89-1.20), and 1.36 (95% CI 1.18-1.58) and melanoma cohorts revealing an adjusted RR of 1.10 (95% CI 0.95-1.27), 0.63 (95% CI 0.47-0.85), and 0.96 (95% CI 0.57-1.62). A total of 5% (2/39) of the studies reported an association among nonmelanoma skin cancers, hepatic cancer, and thyroid carcinomas, with nonmelanoma skin cancer cohorts revealing an adjusted RR of 1.36 (95% CI 1.26-1.47) and 2.66 (95% CI 1.53-4.61), hepatic cancer cohorts revealing an adjusted RR of 1.42 (95% CI 1.06-1.90) and 1.32 (95% CI 0.89-1.95), and thyroid carcinoma cohorts revealing an adjusted RR of 1.06 (95% CI 0.68-1.65) and 1.59 (95% CI 1.07-2.36). Only 1 cohort reported an association with glioma, revealing an adjusted RR of 1.36 (95% CI 1.18-1.58). According to our review, patients with rosacea were statistically more likely to have nonmelanoma skin cancers, breast cancer, and glioma. Rosacea was not found to be substantially associated with melanoma. The associations between rosacea and hepatic and thyroid cancers were unclear because of conflicting results. CONCLUSIONS: The current literature shows that rosacea is significantly associated with increased odds of nonmelanoma skin cancers, glioma, and breast cancer. Rosacea does not appear to be associated with melanoma. Further studies should be conducted to clarify the association between thyroid and hepatic cancers and rosacea.

A rare case of a long-standing, extensive and invasive conjunctival melanoma without systemic metastasis.

Conjunctival melanoma is an uncommon and malignant tumor of the ocular surface with the propensity for metastasis and death. Despite the grim outlook, the factors predicting poor prognosis are slowly being uncovered given the rarity of the disease. Here, we present a rare and surprising case of a long standing, extensive, and invasive conjunctival melanoma that, despite multiple factors predicting a poor prognosis, had no systemic metastatic disease. We hope that by reviewing in depth the various factors that may explain our patient's unusual course of illness we can add to our growing understanding of conjunctival melanoma.

Attenuation of Human Growth Hormone-Induced Rash With Graded Dose Challenge.

Adult growth hormone (GH) deficiency is rare and requires replacement with extrinsic/synthetic injection. GH hypersensitivity has been reported; specifically, atopic patients may develop rashes from somatotropin therapy. Allergic and non-allergic skin reactions to recombinant human GH are uncommon and infrequently reported. We describe a graded-dose challenge with intravenous Norditropin® in a 65-year-old atopic adult woman who developed a severe whole-body rash with Norditropin FlexPro® administration on several occasions but was negative on skin-prick testing to Norditropin® percutaneously and intradermally, but the patch testing was positive for gold and nickel. The patient was registered as a direct admission to the emergency room at a university hospital for a rapid antigen coronavirus disease 2019 (COVID-19) testing after having received two COVID-19 vaccinations and re-testing four months after vaccination. She was then directly admitted to a non-COVID-19 intensive care unit with direct bedside supervision by a registered nurse and a physician board certified in internal medicine, allergy/immunology, and pulmonary diseases. The patient brought a Norditropin® pen which our pharmacy team attached to a compatible syringe for dilutions. A graded dose challenge at a final dosage of 0.1 mL was performed and the patient was monitored for allergic and other adverse drug reactions, which did not occur. At the time of writing this case report, the patient has been maintained on Norditropin FlexPro® 0.1 mL and has not experienced any adverse reactions, including recurrent skin eruptions. The case presented is the first to describe a patient who successfully tolerated a graded dose challenge of an adult patient to GH replacement therapy (as Norditropin®) under supervision in an intensive care unit, whereas prior to reporting of this case, a graded dose challenge to GH replacement therapy had only been successfully performed in a child using another formulation of somatotropin (Humatrope®). Hence, this case lends support that graded dose challenge with somatotropin analogs may be considered for patients with isolated GH deficiency such as in the case presented here.

CK20/CK7 double-negative Merkel cell carcinoma in situ: A case report.

An 83-year-old male with a history of both melanoma and non-melanoma skin cancers presented with a light pink non-ulcerated slightly raised 0.6 × 0.5-cm papule on his left lower extremity. Biopsy specimen revealed a proliferation of intraepidermal round blue cells. On immunohistochemical staining, CD56, chromogranin, and pancytokeratin were faintly positive within the lesional population, while synaptophysin was strongly positive. CD45, CK5/6, CK7, CK20, Melan-A, SOX10, and TTF-1 stains were negative. There was no dermal component identified. A Merkel cell polyomavirus stain was negative. Distant metastases and other in situ pathologies were excluded and a diagnosis of Merkel cell carcinoma in situ (MMCIS) was made. The majority of MCCIS lesions reported in the literature have been discovered amongst other non-melanoma neoplasms. Our findings of an MCCIS with purely intraepidermal involvements without the association with another squamous cell neoplasm is rare finding.

SARS-CoV-2/COVID-19 and its relationship with NOD2 and ubiquitination.

COVID-19 infection activates the immune system to cause autoimmune and autoinflammatory diseases. We provide a comprehensive review of the relationship between SARS-CoV-2, NOD2 and ubiquitination. COVID-19 infection partly results from host inborn errors and genetic factors and can lead to autoinflammatory disease. The interaction between defective NOD2 and viral infection may trigger NOD2-associated disease. SARS-CoV-2 can alter UBA1 and abnormal ubiquitination leading to VEXAS syndrome. Both NOD2 and ubiquitination play important roles in controlling inflammatory process. Receptor interacting protein kinase 2 is a key component of the NOD2 activation pathway and becomes ubiquitinated to recruit downstream effector proteins. NOD2 mutations result in loss of ubiquitin binding and increase ligand-stimulated NOD2 signaling. During viral infection, mutations of either NOD2 or UBA1 genes or in combination can facilitate autoinflammatory disease. COVID-19 infection can cause autoinflammatory disease. There are reciprocal interactions between SARS-CoV-2, NOD2 and ubiquitination.

Intranodal Neurofibroma: A Case Report and Literature Review.

PURPOSE: To report a case of neurofibroma involving the lymph nodes and to perform a literature review on this topic. OBSERVATIONS: A 72-year-old woman with a history of neurofibromatosis and biopsy-proven malignant melanoma of the left forearm underwent wide local excision of the malignant lesion along with sentinel axillary lymph node biopsy. Histological examination of axillary nodes revealed diffuse neurofibromatosis within 2 lymph node capsules. A thorough review of the English literature pertaining to intranodal neurofibroma was performed by querying Google Scholar and PubMed. Only 5 cases of intranodal neurofibroma have been described until now. CONCLUSIONS AND IMPORTANCE: Neurofibroma involving the lymph nodes is rare and this is the first reported case that is shown to diffusely involve the intracapsular space. Furthermore, intranodal neurofibroma can represent a diagnostic pitfall in the evaluation of sentinel lymph nodes for metastatic melanoma.

Vitiligo and Metabolic Syndrome: Systematic Review and Meta-Analysis.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various skin conditions including vitiligo. However, the association between these 2 conditions has yet to be determined by quantitative meta-analysis. OBJECTIVE: The aim of this paper was to determine the association between vitiligo and metabolic syndrome via systematic review and meta-analysis. METHODS: A systematic literature search of Pubmed, Embase, Cochrane, and Web of Science was performed for all published literature prior to August 16, 2020. Case control and prospective cross-sectional studies analyzing the association between vitiligo and MetS were included in this review. The primary outcome measures include the type of vitiligo, diagnostic criteria for MetS, components of MetS (waist circumference, blood pressure, triglycerides, fasting glycemic index, and high-density lipoprotein cholesterol), low-density lipoprotein cholesterol levels, and BMI. A meta-analysis was performed to evaluate the prevalence and association of MetS in patients with vitiligo. RESULTS: A total of 6 studies (n=734 participants) meeting eligibility criteria were included for systematic review and meta-analysis. The pooled prevalence of MetS in patients with vitiligo was (0.296, 95% CI 0.206, 0.386; P<.001). Patients with vitiligo were no more likely to develop MetS compared to control patients (odds ratio 1.66, 95% CI 0.83, 3.33; P=.01). A leave-one-out sensitivity analysis showed a significant association between MetS and vitiligo (P<.001). Significant elevations in fasting glycemic index (mean difference 5.35, 95% CI 2.77, 7.93; P<.001) and diastolic blood pressure (mean difference 1.97, 95% CI 0.02, 3.92; P=.05) were observed in patients with vitiligo compared to control patients. CONCLUSIONS: The association between vitiligo and metabolic syndrome carries important clinical implications. Dermatologists and other multidisciplinary team members should remain vigilant when treating this patient population in order to prevent serious cardiovascular complications that may arise as a result of metabolic disease.

Merkel cell carcinoma in the setting of hematologic disease is associated with unique features and potential pitfalls.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin, often associated with polyomavirus and ultra-violet light exposure. Immunosuppression is associated with increased risk of development of MCC, including that associated with hematolymphoid disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We sought to determine whether MCC arising in patients with hematologic disorders showed unique features. Searching archived material at three institutions, we identified 13 patients with MCC and at least one hematologic malignancy and 41 patients with MCC with no reported hematologic malignancy. CLL/SLL was the most common hematologic disorder in this setting (9/13 cases). Clinical history, variation in morphologic appearance, unusual site distribution and concern for progression of underlying hematologic disease all contributed to potential diagnostic challenges. Overlapping marker expression between MCC and hematologic neoplasms created potential diagnostic pitfalls (e.g. CD138, Pax5, TdT, Bcl2, CD56, and CD117). In addition, we newly identify expression of CD5 and LEF-1 in a subset of MCC, including in patients with CLL/SLL. MCC in patients with hematologic malignancy were more common in men (92% versus 59%, p < 0.05) and showed an unusual site predilection to non-sun exposed sites (3/13 on the buttocks) with none presenting on the face or scalp. By contrast, face or scalp lesions were common in MCC without an associated hematologic malignancy (17/41, p < 0.05). Our findings reaffirm the need for skin surveillance in the setting of immune deficiency and for vigilance to identify unusual presentations of MCC in patients with or without hematologic disorders.

Development of Fulminant Type 1 Diabetes Mellitus in a Patient with DRESS Syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease's myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.

Screening and Intervention for Skin Cancer in the Galapagos.

OBJECTIVE: This study aimed to assess the general dermatological needs and correlation of tentative skin cancer screening diagnoses with histopathological confirmation in the highly sun-exposed locals of the Galapagos Islands. METHODS: An institutional review board-approved prospective study was performed at Blanca's House, a nonprofit surgical volunteer organization, free clinics in the Galapagos. After consent, a 40-item modified SPOTme-inspired questionnaire was completed. Partial or total body skin examinations were conducted by board-certified dermatologists. Board-certified plastic and general surgeons performed excisional biopsies on suspicious lesions. Individuals younger than 18 years, and non-Spanish or non-English speakers were excluded. RESULTS: A total of 273 patients were included in the study, of which 202 reported skin concerns. Benign nevi (n = 76), seborrheic keratosis (n = 42), melasma (n = 19), actinic keratosis (n = 16), acne (n = 15), eczema (n = 13), fungal infections (n = 12), seborrheic dermatitis (n = 5), and psoriasis (n = 5) were most commonly identified.Twelve patients (4.4%) had presumptive skin cancer after screening. Six of 8 biopsies confirmed cancer (group 1), 2 declined a biopsy and 2 were unresectable. Seven basal cell carcinomas and one squamous cell carcinoma were excised with clear margins. A right lower eyelid melanoma was diagnosed and subsequently treated in the United States where invasive melanoma with a Breslow thickness of 0.3 mm was found.Compared with the noncancer group (group 2: n = 265), group 1 had significantly higher likelihood of reporting having seen a dermatologist (P = 0.02), taking any medications (P = 0.0001), having blonde or red hair (P = 0.01), having blue or green eyes (P < 0.0001), and having used indoor tanning equipment (P < 0.0001). Group 1 was also more likely to report 4 or more blistering sunburns (P = 0.08), which approached significance. When evaluated by a dermatologist, group 1 was significantly more likely to be classified as "high risk" for developing cancerous lesions (P < 0.0001) compared with group 2. CONCLUSIONS: Skin concerns in the Galapagos included benign and malignant conditions. There is a need for dermatological care in this medically underserved population. This modified SPOTme-inspired skin cancer questionnaire, confirmed by histology, is a useful tool in identifying high-risk patients and detecting skin cancer in international communities that would have otherwise experienced delays in diagnosis or treatment.

Nodules on the Nasal Tip: Think Before You Laser

Cosmetic consultations are routinely part of a dermatologist's day. Often, patients present after consultation from another dermatologist or other physician with an established diagnosis and would like a particular treatment to resolve their condition. However, it is imperative to take a full history and physical exam prior to rendering treatment in the event of a missed or new diagnosis.

Giant aneurysmal benign fibrous histiocytoma (dermatofibroma).

Aneurysmal benign fibrous histiocytomas are variants of dermatofibromas. These benign blood-filled lesions can mimic malignancies due to their rapid and recurrent growth. Our patient is a 42-year-old Caucasian female with a past medical history of morbid obesity, diabetes, and hypertension, who presented with a mass on her left shoulder for 5 years' duration. The mass oozed occasionally and would appear to regress but then recur replaced with progressively larger masses. Upon inspection, the patient had a large pedunculated exophytic mass with vascularity. The mass was surgically removed under general anesthesia via wide local excision. Grossly, the excised skin was purple-tinged with an underlying fungating solid mass measuring 8.5 cm. Serial sections revealed a hemorrhagic, spongy, and granular cut surface. Histologically, the epidermis was hyperplastic, with underlying hyaline collagen bundles. The remainder of the mass was chronically inflamed and composed of spindled histiocytes, hemosiderin-laden macrophages, and blood-filled spaces lacking an endothelial lining. There was focal pleomorphism but no significant atypia. Immunohistochemical stains were strongly positive for vimentin and negative for CD31, CD34, and desmin. The overall architecture and immunophenotype are consistent with the diagnosis of aneurysmal benign fibrous histiocytoma.

A nongrading histologic approach to Clark (dysplastic) nevi: A potential to decrease the excision rate.

BACKGROUND: Despite a lack of evidence that dysplastic nevi are precursors to melanoma, a large proportion of dermatologists continue to treat them as such. Emerging data suggest that histologic grading approach may result in many unnecessary excisions. OBJECTIVE: Using a nongrading approach to diagnosis of Clark/dysplastic nevi, the current study sought to define and determine the diagnostic uncertainty rate, and to report on the results of re-excisions of such lesions. METHODS: All melanocytic nevi submitted to an academic dermatopathology laboratory between January 1, 2007, and December 31, 2013, were categorized. The number of Clark nevi recommended for re-excision divided by the total number of Clark nevi was taken to be the diagnostic uncertainty rate. RESULTS: This nongrading approach resulted in an excision recommendation/diagnostic uncertainty rate of 11.1%. In 2% of the excised specimens, the diagnosis was changed to melanoma. LIMITATIONS: The study was performed at a single institution, and assigned diagnoses could not be verified other than by the diagnosing dermatopathologists. Lesions that were not submitted as re-excision specimens could have altered the results had they been available for evaluation. CONCLUSION: Compared with previously reported excision rates, the current study shows that the nongrading approach to Clark nevi results in a lower excision rate while still maintaining a low rate of change in diagnosis similar to the grading approach.