Pediatric dermatofibromas: Truncal predominance in younger children.

Pediatric dermatofibromas are considered rare in young children and have not been well characterized, often misdiagnosed clinically. We performed a retrospective case series of children younger than 18 years with histopathologically diagnosed dermatofibromas at our institutions and evaluated age at onset and diagnosis, sex, lesion location, and size, associated symptoms, change over time, and pre-biopsy diagnosis. Overall, dermatofibromas were most common on the back and chest (20/53; 38%), followed by the legs (15/53; 28%) and arms (12/53; 23%) with the most common pre-biopsy diagnosis of "cyst" (23/53; 43%), followed by dermatofibroma (16/53; 30%), and pilomatricoma (12/53; 23%). Our study reinforces previous findings of truncal predominance of pediatric dermatofibromas, different from adults.

Superficial hemosiderotic lymphovascular malformation (hobnail hemangioma): a report of six cases.

Hobnail hemangioma (HH), initially termed targetoid hemosiderotic hemangioma, is a rare, often solitary lesion classically characterized by a central brown or violaceous papulonodule surrounded at times by an ecchymotic halo. This lesion is typically found on the trunk or limbs of children or young to middle-aged adults. Numerous case reports have found HHs to have a reproducible histologic appearance. Although the exact histogenesis of these lesions is unknown, multiple recent immunohistochemical studies suggest a lymphatic origin of these lesions. We present six cases of children with HHs with classic histology but with variability in their clinical appearance. Because the clinical presence of a targetoid halo is inconsistent and the hobnail phenomenon is not specific, we favor the designation of superficial hemosiderotic lymphovascular malformation instead of HH or targetoid hemosiderotic hemangioma as a more unifying term for this rare clinical entity. By eliminating confounding terminologies (in this case, incorporation of "hemangioma" in the name of this entity), we also hope to encourage a swifter change in practice to move away from erroneous diagnostic considerations.

Toxic epidermal necrolysis due to voriconazole: case report and review.

Toxic epidermal necrolysis is an uncommon but potentially life-threatening adverse cutaneous drug reaction characterized by variable degrees of epidermal necrosis and detachment leading to morbidity and risk of mortality. We describe a 67-year-old woman who underwent allogeneic peripheral blood stem cell transplantation as treatment for chronic lymphocytic leukemia. She developed toxic epidermal necrolysis after she was transitioned to voriconazole, which was a component of her post-transplant regimen. The diagnosis of toxic epidermal necrolysis in our patient was made clinically and confirmed histologically. Based on the temporal initiation of voriconazole therapy and the development of her adverse cutaneous reaction, we concluded that voriconazole was the offending agent. There are limited reported cases of voriconazole-induced toxic epidermal necrolysis; we report this case to increase awareness of this potential life-threatening complication.

Updates in atopic dermatitis for the primary care physician: A review of advances in the understanding and treatment of atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin condition occurring in both pediatric and adult patients. Pruritus is a clinical hallmark of the disease, and patients with AD often experience disruptions to their quality of life. The pathogenesis of AD is a complex and multifactorial interplay between genetic factors, epidermal barrier disruption, and immune dysregulation. Clinically, AD is characterized by pruritus, eczematous skin changes, and age-specific lesion distribution patterns. Infants and young children tend to have AD lesions on their face and extensor surfaces of their extremities while older children and adults tend to have AD lesions on flexural surfaces of their extremities. Many patients also experience a chronic and relapsing disease course. Due to the chronicity and severe pruritus, lesions often undergo secondary changes like lichenification. Patients with AD can experience a number of comorbidities including other atopic disease (i.e. allergic rhinitis, asthma), skin infections, cardiovascular, and neuropsychiatric illnesses. Management of AD depends on the severity of the disease as well as the distribution of the disease. Traditionally, treatment of AD included the use of moisturizers / emollients, topical corticosteroids or topical calcineurin inhibitors, or systemic therapy with non-selective immunosuppressants such as corticosteroids, cyclosporine, azathioprine, or similar. However, in the past decade, new biologic and small molecule drugs, both topical and systemic, have become important therapeutic options for AD patients, especially for those with moderate-to-severe disease. The development of these medications, following decades of research to better understand AD, are designed to specifically target various components of immune dysregulation and inflammation implicated in the pathogenesis of AD. Their successful development and deployment now allow for an exciting new era of treatment for individuals suffering from atopic dermatitis.

Algorithms outperform metabolite tests in predicting response of patients with inflammatory bowel disease to thiopurines.

BACKGROUND & AIMS: Levels of the thiopurine metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine commonly are monitored during thiopurine therapy for inflammatory bowel disease despite this test's high cost and poor prediction of clinical response (sensitivity, 62%; specificity, 72%). We investigated whether patterns in common laboratory parameters might be used to identify appropriate immunologic responses to thiopurine and whether they are more accurate than measurements of thiopurine metabolites in identifying patients who respond to therapy. METHODS: We identified 774 patients with inflammatory bowel disease on thiopurine therapy using metabolite and standard laboratory tests over a 24-hour time period. Machine learning algorithms were developed using laboratory values and age in a random training set of 70% of the cases; these algorithms were tested in the remaining 30% of the cases. RESULTS: A random forest algorithm was developed based on laboratory and age data; it differentiated clinical responders from nonresponders in the test set with an area under the receiver operating characteristic (AUROC) curve of 0.856. In contrast, 6-TGN levels differentiated clinical responders from nonresponders with an AUROC of 0.594 (P < .001). Algorithms developed to identify thiopurine nonadherence (AUROC, 0.813) and thiopurine shunters (AUROC, 0.797) were accurate. CONCLUSIONS: Algorithms that use age and laboratory values can differentiate clinical response, nonadherence, and shunting of thiopurine metabolism among patients who take thiopurines. This approach was less costly and more accurate than 6-TGN metabolite measurements in predicting clinical response. If validated, this approach would provide a low-cost, rapid alternative to metabolite measurements for monitoring thiopurine use.

Identification of symptom domains in ulcerative colitis that occur frequently during flares and are responsive to changes in disease activity.

BACKGROUND: Ulcerative colitis disease activity is determined by measuring symptoms and signs. Our aim was to determine which symptom domains are frequent and responsive to change in the evaluation of disease activity, which are those defined by three criteria: 1) they occur frequently during flares; 2) they improve during effective therapy for ulcerative colitis; and 3) they resolve during remission. METHODS: Twenty-eight symptom domains, 16 from standard indices and 12 novel domains identified by ulcerative colitis patient focus groups, were evaluated. Sixty subjects with ulcerative colitis were surveyed, rating each symptom on the three criteria with a 100 mm Visual Analogue Scale. Frequent and responsive symptoms were defined a priori as those whose median Visual Analogue Scale rating for all 3 criteria was significantly greater than 50. RESULTS: Thirteen of the 28 symptom domains were identified as both frequent in ulcerative colitis flares and responsive to changes in disease activity. Seven of these 13 symptom domains were novel symptoms derived from ulcerative colitis patient focus groups including stool mucus, tenesmus, fatigue, rapid postprandial bowel movements, and inability to differentiate liquid or gas from solid stool when rectal urgency occurs. Ten of the 16 symptom domains from standard indices were either infrequent or unresponsive to changes in disease activity. CONCLUSION: Only some of the symptoms of ulcerative colitis that are important to patients are included in standard indices, and several symptoms currently measured are not frequent or responsive to change in ulcerative colitis patients. Development of survey measures of these symptom domains could significantly improve the assessment of disease activity in ulcerative colitis.

Noninvasive ultrasound elasticity imaging (UEI) of Crohn's disease: animal model.

Inflammation occurs in episodic flares in Crohn's disease, which are part of the waxing and waning course of the disease. Healing between flares allows the intestine to reconstitute its epithelium, but this healing results in the deposition of fibrotic scar tissue as part of the healing process. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine. Patients are treated empirically with steroids, with their many side effects, in the hope that they will respond. Many patients would be better treated with surgery if we could identify which patients truly have intestinal fibrosis. Ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and management of local tissue elastic property, particularly intestinal fibrosis. This method allows complete characterization of local intestine tissue with high spatial resolution. The feasibility of UEI on Crohn's disease is demonstrated by directly applying this technique to an animal model of inflammatory bowel disease (IBD). Five female Lewis rats (150-180g) were prepared with phosphate buffered solution (PBS) as a control group and six were prepared with repeated intrarectal administration of trinitrobenzenesulfonic acid (TNBS) as a disease group. Preliminary strain measurements differentiate the diseased colons from the normal colons (p < 0.0002) and compared well with direct mechanical measurements and histology (p < 0.0005). UEI provides a simple and accurate assessment of local severity of fibrosis. The preliminary results on an animal model also suggest the feasibility of translating this imaging technique directly to human subjects for both diagnosis and monitoring.

Postpartum eruption of enoxaparin-induced erythema multiforme.

Enoxaparin is a commonly used hospital medication and in rare instances may result in development of erythema multiforme. Management of these patients can be challenging. Physicians must maintain a high index of suspicion and consider the indication for enoxaparin therapy prior to withdrawal of the medication.

Development of Pityriasis Amiantacea after Valproic Acid Therapy.

Here, we present the case of a 16-year-old male who developed pityriasis amiantacea (PA) after the use of valproic acid. We propose that the keratinocyte proliferative activity of valproic acid mediated through the inhibition of glycogen synthase kinase-3ß, and subsequent activation of the Wnt/ß-catenin pathway could play a role in the development of PA. We additionally review the most relevant characteristics of this disease.

Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).

The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors.

Spironolactone and colitis: increased mortality in rodents and in humans.

BACKGROUND: Crohn's disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation. METHODS: In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF-ß)-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). RESULTS: Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n = 390 deaths, P < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51-2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50-2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82-2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use. CONCLUSIONS: We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S.

Patient reported symptoms during an ulcerative colitis flare: a Qualitative Focus Group Study.

BACKGROUND: It has been assumed that the symptoms measured in disease activity indices for ulcerative colitis reflect those symptoms that patients find useful in evaluating the severity of a disease flare. OBJECTIVE: We aimed to identify which symptoms are important to patients and to compare these symptoms with a comprehensive list of commonly measured symptoms to evaluate whether the patient-reported important symptoms are represented in current disease activity indices for ulcerative colitis. METHODS: Qualitative focus group study. RESULTS: Patients in this sample confirmed 15 symptoms but not 11 other symptoms found in common ulcerative colitis activity indices. Patients identified an additional 14 symptoms not included in commonly used ulcerative colitis activity indices, which they believed to be important in evaluating the onset or severity of an ulcerative colitis flare. CONCLUSION: Current indices capture only a portion of the clinical symptoms that are important to patients in an ulcerative colitis flare, and may neither accurately measure nor fully reflect patients' experience of ulcerative colitis. These findings present an opportunity to develop better patient-centered measures of ulcerative colitis.