Navjeet Sidhu-Malik

Vancomycin-associated linear IgA dermatosis: A report of three cases

BACKGROUND Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure. OBJECTIVE We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. METHODS Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition. RESULTS A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. CONCLUSION Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA1 localized to the sublamina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

IMPORTANCE Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00847912.

Granulocytic sarcoma in the absence of myeloid leukemia

Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic precursor cells. It usually occurs in association with leukemia or other myeloproliferative disorders but can occur without overt hematologic disease. We describe a 6-year-old boy with granulocytic sarcoma in the absence of demonstrable hematologic disease and review the literature regarding the diagnosis, clinical associations, and treatment of this condition.

Treatment of Mycobacterium haemophilum infection with an antibiotic regimen including clarithromycin

A patient with rheumatoid arthritis developed ulcerated nodules predominantly on his legs. Skin biopsy and culture demonstrated rheumatoid vasculitis and infection with Mycobacterium haemophilum. Improvement was not seen until clarithromycin was added to his treatment regimen.

Aplastic anemia in a patient with Rothmund-Thomson syndrome.

This report is the first to describe constitutional aplastic anemia in a patient with Rothmund-Thomson syndrome (also called poikiloderma congenitale), a disease characterized by multiple cutaneous and extracutaneous findings. The findings suggest that although Rothmund-Thomson syndrome is a rare disease, vigilance for the development of associated hematologic abnormalities is warranted.

Long-term follow-up of cutaneous changes in siblings with mandibuloacral dysplasia who were originally considered to have hereditary sclerosing poikiloderma

Mandibuloacral dysplasia is a rare syndrome characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicles, abbreviated, club-shaped terminal phalanges, acroosteolysis, atrophy of the skin over the hands and feet, and poikilodermatous skin changes. We describe the cases of two siblings with features of mandibuloacral dysplasia who as children were considered to have hereditary sclerosing poikiloderma. On their reevaluation as adults, the clinical features of their condition were perceived to be compatible with mandibuloacral dysplasia.

Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: A randomized clinical trial

Importance Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration clinicaltrials.gov Identifier: NCT00847912

Ehlers–Danlos Syndromes

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized clinically by skin fragility, skin hyperextensibility, joint hypermobility, and excessive bruising. At least 10 different subtypes of EDS have been classified based on genetic, biochemical, and clinical characteristics. Recent advances in the molecular analysis of EDS have identified defects responsible for EDS IV (mutations in the type III collagen gene), EDS VI (homozygous and compound heterozygous mutations in the lysyl hydroxylase gene), EDS VIIA and VIIB (mutations in the type I collagen genes), EDS VIIC (deficiency of procollagen N-proteinase), and EDS IX (decreased lysyl oxidase activity). Very little is known about the genetic or biochemical defects responsible for the other EDS subtypes, but with the application of the tools of molecular biology, analysis of these defects is now within reach.