First report of mesalamine (5-aminosalicylic acid) as the causative agent in a case of acute generalized exanthamous pustulosis.

Acute generalized exanthamous pustulosis (AGEP)is a rare eruption of non-follicular sterile pustuleson a diffuse background of erythema and edema,commonly associated with fever and leukocytosis.Antibiotics are implicated in most cases; however,other drugs have been reported to cause AGEP. Wereport a case of a 73-year-old man with a historyof ulcerative colitis who presented with a diffusepustular rash, renal failure, elevated liver functiontests, and leukocytosis with neutrophilia. A week priorto admission, the patient was started on mesalamineto treat colitis. Upon admission, a workup includinga skin biopsy was performed and was consistentwith AGEP. Mesalamine was discontinued, and thepatient's skin eruption, renal function, liver functiontests, and leukocytosis subsequently improved.Mesalamine has an unknown mechanism of action.However, it is thought to be an anti-inflammatoryagent that blocks the production of leukotrienesand prostaglandins and is an immunosuppressantthat increases the release of adenosine, whichinterferes with leukocyte function. The decrease inprostaglandin synthesis or deregulation of leukocytefunction caused by mesalamine may be the etiologyin this case. Discontinuation of the offending agentleads to resolution of AGEP, as it did in this patient.

Novel Use of Preoperative Epidermal Coloring of Very Small Dermatological Specimens-Protocol for Reduction of Lost Specimens.

Small tissue biopsies are often difficult to visualize and can be easily lost or mishandled. The authors hypothesized that full epidermal surface coloration of small skin lesions with a sterile skin marker (gentian violet ink) before performing shave biopsy would make small gross specimens easier to identify without impacting microscopic appearance. Live evaluation of 4 inked and 4 noninked gross (2-3 mm) specimens in covered and uncovered formalin-containing jars by 50 consecutive health care personnel demonstrated that inked specimens were significantly (P < 0.001) easier to visualize than noninked specimens. Additionally, a blinded dermatopathologist evaluated 25 inked and 25 noninked specimens microscopically. Utilization of this inking process did not interfere with histopathologic assessment or impede diagnosis. This pilot study describes an easily implementable quality improvement measure that may decrease the rate of loss and mishandling of specimens.

The Value of the Black Box Warning in Dermatology.

Boxed, or "black box" warnings are issued by the United States Food and Drug Administration (US FDA) as a means to label drugs associated with serious adverse events. However, there is no clear metric to determine how and when the boxed warning is applied. Inconsistencies in the review process, language, timing, and dissemination of these warnings impact dermatologists and their patients. Appropriate patient selection and monitoring can help minimize risk to patients when prescribing drugs with boxed warnings. Future changes in the manner in which the boxed warning is issued and in its subsequent clinical application may improve the utility of these warnings for dermatologists and ultimately, patient safety.

Resolution of recalcitrant pyogenic granuloma with laser, corticosteroid, and timolol therapy.

A pyogenic granuloma (PG) is a rapidly growing benign vascular tumor that can be found on the skin or subcutaneous tissue. While some pyogenic granulomas may resolve spontaneously, most have a tendency to bleed easily and require treatment. Current therapeutic modalities include topical imiquimod, cryotherapy, electrodessication, curettage, excision, laser therapy, sclerotherapy, and microembolization. We report a recalcitrant case of chronic pyogenic granuloma occurring on the scalp of a healthy young male which was unresponsive to conventional surgical and non-surgical modalities. Ultimately, aggressive laser therapy, intralesional triamcinolone acetonide injections, and topical timolol application led to complete resolution and healing.

Calciphylaxis: a systematic review of existing and emerging therapies.

Calciphylaxis, also known as calcific uremic arteriolopathy, is a cutaneous ischemic small vessel vasculopathy seen in 1 to 4% of patients with chronic kidney disease on hemodialysis. It is associated with extreme pain and a 60 to 80% mortality rate in the setting of few and frequently ineffective therapeutic options, although this may be changing based on reports of success with newer therapies.

Skin cancer discovery during total body skin examinations.

BACKGROUND: Patients presenting with a site-specific skin complaint may receive a total body skin examination (TBSE) or a more focused examination. A TBSE may be time-consuming but can potentially detect unsuspected or early stage skin cancers. The purpose of this study was to assess the detection of skin cancers associated with dermatologist-initiated TBSE performed immediately after a focused skin examination on the same patients. METHODS: The dermatology records of patients with biopsy-proven melanoma, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC) during a 2-year period were reviewed. Generalized linear mixed-effects models were used to estimate the odds of a lesion being identified by a dermatologist (rather than the patient or the patient's primary health care provider). RESULTS: A total 1563 biopsy-proven cutaneous malignancies were found on 1010 patients. Of these, 797 cancers (51%) were first identified by a dermatologist on TBSE and 764 (48.9%) by the patient or the referring provider. Among tumors first identified by dermatologists (n = 797), 553 (69%) were BCCs, 220 (28%) were SCCs, and 24 (3%) were melanomas. The mean Breslow depth was 0.53 mm (standard deviation: 0.31 mm) for melanomas found on TBSE versus 1.04 mm (standard deviation: 1.68 mm) if identified by patients or referring providers. BCCs were more likely to be identified by a dermatologist during a TBSE (n = 553 [56%] vs. n = 434 [44%]; odds ratio: 1.79; p < .001). Tumors ultimately diagnosed as SCCs were more often identified by patients or patients' primary care providers (n = 302 [58%]; odds ratio: 0.56; p < .001). However, 220 otherwise undetected SCCs were found during dermatologist-performed TBSE. CONCLUSION: Dermatologist-performed TBSEs identified numerous cutaneous malignancies that might otherwise have remained undiagnosed. Early detection of melanoma or nonmelanoma skin cancer by TBSEs may spare patients significant morbidity and mortality.

Delay in Diagnosis of Celiac Disease in Patients Without Gastrointestinal Complaints.

PURPOSE: The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs nongastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder that affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations; it can be characterized by predominately gastrointestinal symptoms, or it may present without any gastrointestinal symptoms. METHODS: We retrospectively reviewed the charts of 687 adult patients who carried the diagnosis of celiac disease. Patients included had biopsy-proven celiac disease and were categorized based on presence or absence of gastrointestinal symptoms prior to their diagnosis. RESULTS: There were 101 patients with biopsy-proven celiac disease that met inclusion criteria. Fifty-two patients presented with gastrointestinal symptoms and 49 had nongastrointestinal complaints. Results from Mann-Whitney statistical analysis showed a median delay in diagnosis of 2.3 months for the gastrointestinal symptoms group and 42 months for the nongastrointestinal group (P <.001); 43.2% of patients with nongastrointestinal symptoms had abnormal thyroid-stimulating hormone, as opposed to 15.5% in the gastrointestinal symptom group (P = .004). Of patients with nongastrointestinal symptoms, 69.4% had anemia, compared with 11.5% of the gastrointestinal symptom group (P <.001). The majority of patients in the nongastrointestinal symptom group, 68%, were noted to have abnormal bone density scans, compared with 41% in the gastrointestinal symptom group. No sex differences were noted on chi-squared analysis between the 2 groups (P = .997). CONCLUSIONS: Although there is growing awareness of celiac disease, the delay in diagnosis for patients without gastrointestinal symptoms remains prolonged, with an average delay of 3.5 years.

A Retrospective Analysis of Surveillance Adherence of Patients after Treatment of Primary Cutaneous Melanoma.

BACKGROUND: Melanoma surveillance serves to identify new primary melanomas and curable locoregional or early distant recurrences. Although an optimal melanoma surveillance strategy has not been determined, several clinical guidelines exist. OBJECTIVE: The aim of this study was to identify demographic and clinico-pathologic variables associated with poor adherence to National Comprehensive Cancer Network (NCCN) melanoma surveillance guidelines. DESIGN: We retrospectively reviewed the initial five-year dermatology follow-up visit frequencies of melanoma patients and extracted basic demographic and clinical data from their medical records. PARTICIPANTS: Of 186 patients included, the mean age was 55 (standard deviation=15); 47.5 percent (n=85) were female, 93.0 percent (n=173) were white, and 76.2 percent (n=141) were married. Sixty percent of patients lived at locations more than 10 miles from the clinic, and 58.6 percent had private insurance. MEASUREMENTS: "Aggressive" and "conservative" surveillance schedules were adapted from National Comprehensive Cancer Network visit frequency guidelines. RESULTS: Between 58.4 and 74.5 percent of patients adhered to "aggressive" surveillance, with decreasing rates over the five-year period. Annual rates of poor surveillance adherence (7.3-23.6%) increased over time. Based on adjusted odds ratios, patients younger than 50 years of age (odds ratios 2.11 [95% CI 1.13-3.93], p<0.05), those lacking health insurance (odds ratios 3.08 [95% CI 1.09-8.68], p<0.05), and those with at least Stage IIB disease (odds ratios 3.21 [95% CI 1.36-7.58], p<0.01) are more likely to be poorly adherent to melanoma surveillance. CONCLUSION: This study's findings highlight some variables associated with poor surveillance adherence among melanoma survivors that could help to guide efforts in counseling this at-risk population.

Calciphylaxis: a case series and the role of radiology in diagnosis.

BACKGROUND: Calciphylaxis is a syndrome of vascular calcification most commonly affecting patients with end-stage renal disease (ESRD) on hemodialysis. Because of its high mortality rate, early diagnosis and treatment are necessary. Although diagnosis is usually based on skin biopsy, histopathology is often nonspecific. As the role of imaging in calciphylaxis has not been studied extensively, we examined the utility of radiology in the diagnosis of this disease. METHODS: A thorough review of electronic medical records for 2005-2013 at Loyola University Medical Center yielded 10 patients with biopsy-proven calciphylaxis. Using the radiological picture archiving and communication system (PACS), all imaging studies of the affected body part obtained within 6 months of diagnosis were analyzed and tabulated. RESULTS: All 10 patients had undergone imaging (computed tomography, ultrasound, plain radiography, and/or mammography) of the affected anatomy prior to diagnosis by skin biopsy. Nine of these patients were noted to have moderate-to-severe soft tissue vascular calcification in the area of skin biopsy. CONCLUSIONS: This case series supports the suggestion that findings of superficial vascular calcifications on imaging studies are sensitive for the diagnosis of calciphylaxis. Used in conjunction with histopathological, clinical, and laboratory data, radiology can serve an important role in the diagnosis of calciphylaxis.

Changing paradigms in dermatology: nuclear hormone receptors.

Nuclear hormone receptors (NHRs) are a family of proteins that function similarly as nuclear transcription factors. The NHR family includes glucocorticoid receptors, retinoic acid and retinoid receptors, vitamin D receptors, thyroxin receptors, and peroxisome proliferator activated receptors. These proteins are targets for some of the most commonly prescribed medications in dermatology, including corticosteroids, retinoids, and vitamin D analogues, all of which have limiting side effects. Advances in this field have led to better understanding of the mechanisms of NHR therapeutic and toxic effects, receptor subtypes, tissue distribution, and interaction with other molecules. New generations of more specific NHR ligands designed to increase therapeutic efficacy and limit adverse effects have dramatically expanded the clinical application of NHR-targeting drugs. The current understanding of NHRs and future directions for NHR ligands in dermatology are discussed.

Psoriasis and its treatment with infliximab-mediated tumor necrosis factor alpha blockade.

The pathogenesis of psoriasis, a chronic immune-mediated inflammatory skin disease,involves increased concentrations and activity of several proinflammatory cytokines,including tumor necrosis factor alpha (TNF-alpha). Infliximab is a chimeric human-murine TNF-alpha antibody that selectively blocks the activity of TNF-alpha. In controlled clinical trials, infliximab treatment has produced rapid and sustained improvements in psoriasis lesions and psoriatic joint involvement, with a favorable short-term safety and tolerability profile. Treatment with infliximab may be associated with an increased risk of infection or infusion reaction: however, the side-effect profile of infliximab in patients with psoriasis remains to be fully characterized, and assessment of infliximab in this population is currently ongoing in phase 3 studies. Comprehensive evaluation in controlled trials may allow infliximab to take its place among the expanding group of biologic drugs for the treatment of moderate to severe psoriasis.

Treatment of refractory ulcerative necrobiosis lipoidica diabeticorum with infliximab: report of a case.

BACKGROUND: Necrobiosis lipoidica diabeticorum (NLD) is a rare, granulomatous inflammatory skin disease of unknown origin, sometimes associated with diabetes mellitus. Skin lesions usually develop on the lower extremities and can progress toward ulceration and scarring. Many treatments have been proposed, but few have demonstrated consistent efficacy, and no standard regimens have emerged to date. OBSERVATIONS: An 84-year-old woman with type 1 diabetes mellitus presented with a 3-year history of chronic right-lower-extremity erythematous papules and plaques that had developed into confluent ulcers with prominent granulation tissue and an orange-yellow hue. The results of a biopsy of the lesion was consistent with a diagnosis of NLD. The wound did not respond to 4 months of intensive local wound care. After the first intravenous infusion of infliximab (5 mg/kg), there was rapid reduction in wound size, pain, and drainage. There was complete wound healing with excellent cosmesis at 6 weeks (total of 3 infusions). CONCLUSIONS: Infliximab should be considered in the treatment of refractory, ulcerative NLD. Its anti-tumor necrosis factor activity may underlie its efficacy in targeting this granulomatous process, and further investigation should be undertaken to confirm these results.