Meg R. Gerstenblith

Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours

Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlins syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlins syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.

Update on primary mucosal melanoma

Mucosal melanomas are aggressive cancers of mucosal surfaces with clinical and pathologic characteristics distinct from cutaneous melanomas, warranting different staging systems and treatment approaches. Surgical resection is performed frequently for the primary tumor, although the utility of lymph node surgery and radiation therapy is not established. Therapies targeted against C-KIT activating mutations, identified in many mucosal melanomas, are emerging as promising treatments.

Bullous Lupus: An Unusual Initial Presentation of Systemic Lupus Erythematosus in an Adolescent Girl

Abstract:u2002 Bullous systemic lupus erythematosus is a subepidermal blistering disease that occurs only rarely in a subset of patients with systemic lupus erythematosus and even less commonly in pediatric patients. Autoimmunity in bullous systemic lupus erythematosus is characterized by the presence of circulating anti‐type VII collagen antibodies. We report here a case of a child whose initial systemic lupus erythematosus presentation was a diffuse bullous eruption.

Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins

IMPORTANCEnTo our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions.nnnOBJECTIVESnTo study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility.nnnDESIGN, SETTING, AND PARTICIPANTSnIdentical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated.nnnMAIN OUTCOMES AND MEASURESnThe NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists.nnnRESULTSnAmong the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (ru2009=u20090.69 vs ru2009=u20090.46; Pu2009=u2009.04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (ru2009=u20090.38; Pu2009<u2009.001) and lifetime UV radiation exposure (ru2009=u20090.26; Pu2009<u2009.001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (ru2009=u20090.21; Pu2009<u2009.001), smoking (ru2009=u20090.10; Pu2009<u2009.02), alcohol consumption (ru2009=u20090.11; Pu2009=u2009.01), cardiovascular comorbidity (ru2009=u20090.17; Pu2009<u2009.001), and skin cancer comorbidity (ru2009=u20090.19; Pu2009<u2009.001).nnnCONCLUSIONS AND RELEVANCEnThe study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma

Intravascular B-cell lymphoma is a rare type of non-Hodgkins lymphoma that is characterized by a clonal proliferation of lymphoblasts within small blood vessels. Patients present with nonspecific symptoms and are often only given a diagnosis at autopsy. We report a case of intravascular B-cell lymphoma, characterized by pyrexia, anemia, thrombocytopenia, and mental status decline, without obvious cutaneous manifestations, that was diagnosed with blind skin biopsy.

Pompholyx and eczematous reactions associated with intravenous immunoglobulin therapy

INTRODUCTIONnIntravenous immunoglobulin (IVIG) is used to treat many inflammatory and autoimmune disorders and although generally well tolerated, cutaneous side effects occur.nnnOBJECTIVEnWe reviewed reports of pompholyx and eczematous reactions associated with IVIG.nnnMETHODSnA literature search was performed using the PubMed and MEDLINE databases with the search terms intravenous immunoglobulin pompholyx, intravenous immunoglobulin eczema, intravenous immunoglobulin cutaneous adverse effects, intravenous immunoglobulin cutaneous effects, intravenous immunoglobulin skin effects, and intravenous immunoglobulin adverse effects. Relevant English-language articles or articles in other languages cited in English-language articles were included.nnnRESULTSnWe identified 64 cases of eczematous reactions associated with IVIG therapy, including a patient treated on our inpatient consult service. In reported cases, the majority of patients (62.5%) had pompholyx alone or a combination of pompholyx on the hands or feet and two or fewer additional body surfaces involved. The majority of reported cases (75%) experienced the eczematous reaction after their first IVIG treatment. Neurologic conditions were the most common (85.9%) diseases for which IVIG was used. Most patients responded well to topical steroids or did not require treatment.nnnLIMITATIONSnSome reported cases had insufficient descriptions to be included in this review. Axa0literature review may underestimate the frequency of eczematous reactions to IVIG because these reactions are often limited and may not be reported.nnnCONCLUSIONSnWith the use of IVIG increasing, it is important for dermatologists to recognize this cutaneous side effect of IVIG.

Necrolytic Acral Erythema as a Cutaneous Marker of Hepatitis C: Report of Two Cases and Review

Necrolytic acral erythema (NAE) is a member of the necrolytic erythemas, which include necrolytic migratory erythema (NME), acrodermatitis enteropathica, and various dermopathies secondary to nutritional deficiencies. NAE is distinct from the other necrolytic erythemas by virtue of its consistent association with hepatitisxa0C (HCV) together with the acral distribution of its lesions, in particular, dorsal hands and feet. Although its etiology is unknown, NAE has been reported to respond to zinc replacement, suggesting a causal relationship. Two patients with HCV infection presented with scaly acral plaques and histopathologic features consistent with NAE while also demonstrating atypical palmoplantar accentuation of lesions. Both patients were found to have zinc deficiency, and their lesions responded to zinc supplementation. Awareness of NAE as a unique cutaneous marker for HCV infection is important not only for accurate dermatologic diagnosis but also for appropriate management of associated morbidity and prompt detection of potentially undiagnosed underlying HCV.

Granuloma Annulare in the Setting of Ipilimumab Therapy

We present a patient who developed granuloma annulare during ipilimumab therapy. Many adverse events of ipilimumab therapy are well documented, such as rash, colitis, hepatotoxicity, and endocrinopathies [1]. Here, we describe a case of granuloma annulare as a side effect of ipilumumab therapy.

Metastastic vulvar squamous cell carcinoma mimicking genital herpes

Metastatic disease to the skin can be difficult to diagnose clinically because it often mimics many infectious, inflammatory, and neoplastic skin conditions. Cutaneous metastases can present as dermal or subcutaneous nodules, exophytic tumors resembling melanoma or nonmelanoma skin cancer, erythematous patches and plaques resembling erysipelas or eczema, or indurated plaques resembling morphea or scleroderma.1 Rarely, cutaneous metastases present as grouped papulo-vesicles resembling herpes group virus infections.1

Meta-Analyses of Epidemiologic Associations between Cutaneous Melanomaand Thyroid Cancer

Background: The incidences of cutaneous melanoma (CM) and thyroid cancer (TC) continue to increase in the United States, and recent studies have demonstrated associations between these two malignancies. Objective: We explore these associations between CM and TC by reviewing, and combining in meta-analyses, population-based studies that assessed risk for TC in individuals with a history of CM, and reciprocally, risk for CM in individuals with a history of TC. Methods: A literature search was performed using the PubMed databases with the terms “melanoma thyroid cancer.” Relevant English-language articles were included. Meta-analyses were conducted for both risk of TC among CM survivors and CM among TC survivors. Results: Population-based studies demonstrate an increased risk for TC among CM survivors, and likewise, an increased risk of CM among TC survivors. Our meta-analysis suggests a statistically significant standardized incidence ratio (SIR) for TC after CM of 1.88 (95% confidence interval (CI): 1.62-2.15), which was higher among men (2.60, 95% CI=1.65-3.55) compared to women (1.59, 95% CI=1.10-2.09), but this was not statistically significant. Likewise, a significant SIR for CM after TC of 1.49 (95% CI=1.20-1.79) was demonstrated in the metaanalysis; however, the sex-specific SIRs for CM after TC were not statistically significantly different, which may be due to small sample sizes. Conclusions: The observed bidirectional association between CM and TC raises the possibility of shared risk factors, which should be further explored. Additionally, further studies should be performed to assess the benefit of screening TC patients for melanoma and CM patients for TC.