The methotrexate polyglutamate assay supports the efficacy of methotrexate for severe inflammatory skin disease in children.

BACKGROUND: The methotrexate (MTX) polyglutamate assay has been validated in adults with arthritis. OBJECTIVE: We sought to assess clinical response rates and the value of the methotrexate polyglutamate assay in MTX-treated children with inflammatory skin diseases. METHODS: In this retrospective review, 46 MTX-treated children with a diagnosis of atopic dermatitis, psoriasis, or psoriasis-eczema overlap were serially assessed with the methotrexate polyglutamate assay. RESULTS: In all, 38 children (83%) achieved good to excellent response: 27 (59%) within 12 weeks and 11 (24%) after dose-adjustment. Good to excellent responses were highest for psoriasis/overlap: 15 of 16 (94%), compared with 23 of 30 (77%) with atopic dermatitis. Mean maximum polyglutamate levels were 31.5 nmol/L for responders versus 18.1 nmol/L for nonresponders (P = .035). This difference was also significant for the subset with atopic dermatitis, but not for those with psoriasis/overlap. After dose modification, late responders ultimately achieved a significantly higher mean maximum methotrexate polyglutamate assay (41.9 nmol/L) compared with nonresponders (P = .002). LIMITATIONS: Retrospective design and small sample size were limitations. CONCLUSIONS: MTX is an effective treatment for the majority of children with inflammatory skin diseases, but a subset requires dose modification to achieve good to excellent response. Methotrexate polyglutamate assay levels reflect response to treatment, but are most useful to support dose modification among children who fail to respond within 12 weeks.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.

The importance of reviewing pathology specimens before Mohs surgery.

BACKGROUND: The review of outside biopsy slides before performing surgery is the standard of care in many surgical specialties. Previous studies have shown high discrepancy rates between the original and second-opinion diagnoses. The frequency with which this practice changes the diagnosis and management of patients undergoing Mohs surgery is undocumented in the literature. It is standard practice at our institution to review all outside biopsy slides before Mohs surgery. OBJECTIVE: To investigate how often review of outside biopsies by an internal dermatopathologist changes patients' initial referral diagnosis and subsequent management. METHODS & MATERIALS: This is a retrospective review of all patients referred to Mohs surgery from January 2003 through March 2007. The number of cases in which the diagnosis changed and how this change affected management were recorded. RESULTS: Seventy-four of 3,345 (2.2%) cases were identified in which the diagnosis changed after review of the biopsy slides. Management was affected in the majority (61%) of cases. Board-certified dermatopathologists originally read nearly half of the biopsies. CONCLUSION: Review of outside biopsy slides before surgery can change the diagnosis in a large proportion of patients, with a resulting change in management. This quality-assurance practice may improve patient care.

An open-label trial of the efficacy of 15% aluminum chloride in 2% salicylic acid gel base in the treatment of moderate-to-severe primary axillary hyperhidrosis.

Primary focal hyperhidrosis (HH) is a chronic disorder of excessive sweating. A single-center, open-label study was performed to determine the efficacy and safety of 15% aluminum chloride (AC) in 2% salicylic acid gel base (SAGB) Hydrosal in adults with moderate-to-severe primary axillary HH. Thirty subjects were given 15% AC in 2% SAGB to apply to their bilateral axillae nightly for the first week, then twice-weekly application as tolerated. The primary objective was change in mean Hyperhidrosis Disease Severity Score (HDSS) score from baseline to week 4. Participants who achieved an HDSS score < 2 were designated as "responders." Mean change in HDSS from baseline to week 4 was 1.32 (p = 0.0001). At week 4, 21 of 29 (72%) were responders, and at week 12, 18 of 25 (72%) were responders. Based on these results, 15% AC in 2% SAGB may be an effective, high-strength AC topical therapy for treatment of patients with moderate-to-severe axillary HH.

Comparison of alpha- and beta-hydroxy acid chemical peels in the treatment of mild to moderately severe facial acne vulgaris.

BACKGROUND: Chemical peels are used as adjuvants for treatment of facial acne. No well-controlled studies have compared alpha- and beta-hydroxy acid peels in the treatment of mild to moderately severe facial acne. OBJECTIVE: To compare the efficacy of alpha- and beta-hydroxy acid chemical peels in the treatment of mild to moderately severe facial acne vulgaris. MATERIALS AND METHODS: Twenty patients were recruited in this split-face, double-blind, randomized, controlled study. An alpha-hydroxy acid (30% glycolic acid) was applied to one-half of the face and a beta-hydroxy acid peel (30% salicylic acid) was applied contralaterally every 2 weeks for a total of six treatments. A blinded evaluator performed quantitative assessment of papules and pustules. RESULTS: Both chemical peels were significantly effective by the second treatment (p<.05) and there were no significant differences in effectiveness between the two peels. At 2 months posttreatment, the salicylic acid peel had sustained effectiveness. More adverse events were reported with the glycolic acid peel after the initial treatment. CONCLUSION: The glycolic acid and salicylic acid peels were similarly effective. The salicylic acid peel had sustained effectiveness and fewer side effects. Alpha- and beta-hydroxy acid peels both offer successful adjunctive treatment of facial acne vulgaris.

Botulinum toxin type a versus topical 20% aluminum chloride for the treatment of moderate to severe primary focal axillary hyperhidrosis.

Severe hyperhidrosis affects 2.8% of the population and can be emotionally devastating. First-line therapy employs topical agents such as aluminum chloride (AC), but efficacy and tolerability vary widely. Botulinum toxin type A (BTX-A) is FDA-approved for the treatment of primary focal axillary hyperhidrosis unresponsive to topical therapy. A single-center, randomized, parallel, open-label, 12-week study was performed to compare the efficacy and safety of BTX-A with 20% AC for the treatment of primary focal axillary hyperhidrosis. Twenty-five subjects were randomized to either BTX-A or AC treatment, and were evaluated for treatment response by an improvement of > or =2 grades on the Hyperhidrosis Disease Severity Scale (HDSS). At week 4, 92% of the subjects in the BTX-A group achieved treatment response compared with 33% of the subjects in the AC group. Overall, treatment with BTX-A was more effective and provided greater patient satisfaction than with AC. Treatment with AC was effective and tolerated in 29% of the subjects.

Blue-jean button nickel: prevalence and prevention of its release from buttons.

BACKGROUND: Nickel is a common cause of allergic contact dermatitis and is associated with metal buttons and snaps on blue jeans. OBJECTIVE: To determine the prevalence of nickel-positive metal buttons on blue jeans and the efficacy of nail polish in the prevention of nickel release. METHODS: We collected 62 pairs of new and preworn blue jeans. The metal buttons were tested for nickel with a dimethylglyoxime test kit, and one coat of clear nail polish was applied to nickel-positive buttons. Painted buttons were dried for 24 hours, and the jeans were washed on delicate cycle and retested for nickel. The jeans underwent a second wash/dry cycle and were retested. RESULTS: The prevalence of nickel-positive metal buttons on blue jeans was 16%. Ten pairs of jeans tested positive for nickel. All 10 pairs tested negative for nickel after the application of one coat of clear nail polish. Of these 10 pairs, seven pairs underwent two wash/dry cycles, and all seven tested negative for nickel after each cycle. CONCLUSION: The presence of nickel-positive blue-jean buttons is greater in new jeans than in preworn jeans. One clear coat of nail polish can prevent nickel release through two wash/dry cycles in a test environment.

When a hero becomes a patient: firefighter burn injuries in the National Burn Repository.

Firefighters receive significant training and are outfitted with state-of-the-art protective equipment. However, given the unpredictable nature of their work environment, injuries still occur. The National Burn Repository (NBR) was viewed as a resource for defining the epidemiology of these injuries on a national level and to identify predictive factors for outcomes in this population. The NBR was queried for the occupation of "firefighter" for the years 1990-2008. Records were screened for completeness, and 597 patients were identified for analysis. Data examined included demographics, %TBSA burn, length of stay (LOS), injury circumstance, and disposition. Multiple linear regression models were created to determine factors related to outcome measures. The majority of patients were white (84%) and male (96%). The mean age was 35 years. Most injuries were caused by fire/flame (73%). Only six deaths (1%) were reported. Most injuries were work-related (86%), and most patients were discharged home (92%). Inhalation injury was documented in 9% of patients. The mean LOS was 6.5 ± 11.3 days (median 2 days), and few patients had critical care requirements. The average %TBSA was 6 ± 11.7%. Patients with larger injuries had increased LOS. The presence of inhalation injury, elevated carboxyhemoglobin levels, and advancing age were significantly associated with larger burns. From the NBR data, most firefighter burn injuries were small, and few firefighter burn patients required critical care resources or had significant disability. Firefighters comprise a small number of burn center admissions each year, yet they are an important population to consider for burn prevention efforts.

Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis.

Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin-simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.

The results of a national survey regarding nutritional care of obese burn patients.

Little is known about the nutritional needs of obese burn patients. Given the impact of obesity on the morbidity and mortality of these patients, a uniform understanding of perceptions and practices is needed. To elucidate current practices of clinicians working with the obese burn population, the authors constructed a multidisciplinary survey designed to collect this information from practitioners in United States burn centers. An electronic approach was implemented to allow for ease of distribution and completion. A portable document format (pdf) letter was e-mailed to the members of the American Burn Association and then mailed separately to additional registered dietitians identified as working in burn centers. This letter contained a link to a 29-question survey on the SurveyMonkey.com server. Questions took the form of multiple choice and free text entry. Responses were received from physicians, mid-level practitioners, registered dietitians, and nurses. Seventy-five percent of respondents defined obesity as body mass index >30. The Harris-Benedict equation was identified as the most frequently used equation to calculate the caloric needs of burn patients (32%). Fifty-eight percent indicated that they alter their calculations for the obese patient by using adjusted body weight. Calculations for estimated protein needs varied among centers. The majority did not use hypocaloric formulas for obese patients (79%). Enteral nutrition was initiated within the first 24 hours for both obese and nonobese patients at most centers. Sixty-three percent suspend enteral nutrition during operative procedures for all patients. Oral feeding of obese patients was the most preferred route, with total parenteral nutrition being the least preferred. Longer length of stay, poor wound healing, poor graft take, and prolonged intubation were outcomes perceived to occur more in the obese burn population. In the absence of supporting research, clinicians are making adjustments to the nutritional care of obese burn patients. This indicates the need for further research to determine consistent best practices.

EBV-associated recurrent Hodgkin's disease after renal transplantation.

Hodgkin's disease is recognized as part of the spectrum of post-transplantation lymphoproliferative disorders (PTLD), although it is still an uncommon de novo malignancy in this population. Epstein-Barr virus (EBV) has been linked to both post-transplant non-Hodgkin's lymphomas and Hodgkin's disease. We report a case of recurrent Hodgkin's disease in a patient who received a renal transplant in childhood and later developed EBV-associated Hodgkin's disease with remission after chemotherapy until subsequent relapse 9 years later that was successfully treated. To our knowledge, this is the first report of recurrent Hodgkin's disease in a transplant recipient. We briefly discuss the pathogenesis of and risk factors for EBV-related PTLD, utility of EBV load surveillance, and the options for treatment of PTLD including immunosuppression reduction, antiviral therapy, anti-CD20 monoclonal antibodies, cytotoxic T cells, and the possible roles of interferon-alpha and rapamycin.

The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection.

BACKGROUND: While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spectrum of other kidney diseases seen among HIV-infected patients. METHODS: This retrospective cohort study included all HIV-infected patients who underwent renal biopsy during the course of their clinical care at six major medical centers. Demographic and clinical information were abstracted from each patient's clinical record. Time to initiation of renal replacement therapy was compared for patients with lesions other than HIVAN to patients with HIVAN using Cox proportional hazards regression. RESULTS: Eighty-nine patients (47 with lesions other than HIVAN and 42 with HIVAN) were available for inclusion. Patients with lesions other than HIVAN were less likely to be black (37/47 vs. 42/42, P= 0.02), more likely to have a positive hepatitis B surface antigen (10/37 vs. 4/42, P= 0.04), less likely to have the diagnosis of hypertension (24/46 vs. 31/42, P= 0.03), more likely to have a greater creatinine clearance at time of biopsy (60.6 vs. 39.0 cc/min, P= 0.008), and have a greater CD4 lymphocyte count at time of biopsy (287 vs. 187 cells/mL, P= 0.04) compared to patients with HIVAN. Lesions other than HIVAN were associated with a longer time to initiation of renal replacement therapy compared with HIVAN (HR 0.33, 95% CI 0.15-0.71, P= 0.005). Other factors associated with a longer time to renal replacement therapy included higher creatinine clearance at time of biopsy, greater CD4(+) lymphocyte count, the absence of hepatitis C antibody, and the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The type of renal disease (HIVAN vs. other) interacted significantly with HIV-1 RNA level and the use of antiretroviral therapy (P= 0.0001 and 0.006, respectively). Among patients with lesions other than HIVAN, the presence of nondetectable HIV-1 RNA was not associated with a greater risk of progression of renal disease (HR 0.27, P= 0.24). Among patients with HIVAN, because all patients had detectable virus at the time of institution of renal replacement therapy, this highly significant association could not be quantified. Among patients with lesions other than HIVAN, the use of antiretroviral therapy was not associated with the progression to renal replacement therapy (HR 3.29, P= 0.06). Among patients with HIVAN, the use of antiretroviral therapy was associated with a slower progression to renal replacement therapy (HR 0.24, P= 0.03). CONCLUSION: Among HIV-infected patients with renal disease other than HIVAN, viral suppression and the use of antiretroviral therapy are not associated with a beneficial effect on renal function; thus, additional therapeutic strategies may need to be utilized. Because renal histology is associated with prognostic differences, these data provide outcomes information that will improve the clinical utility of renal biopsy among HIV-infected patients with renal disease.