Scott Walsh

Mycosis fungoides in the pediatric population: report from an international Childhood Registry of Cutaneous Lymphoma.

Background/Objectives: There are limited data on the clinical presentation and progression of pediatric cutaneous lymphoma. This study focuses on the clinical characteristics of pediatric patients with mycosis fungoides (MF). Materials and Methods: This descriptive study presents clinical characteristics of 22 pediatric patients with MF, enrolled in the international Childhood Registry for Cutaneous Lymphomas (CRCL). Results: The mean ages at onset and at diagnosis were 7.5 (SD 3.8 years) years and 9.9 (SD 3.4) years, respectively. The most common MF presentation was patch stage (68%), followed by hypopigmentation (59%) and plaque stage disease (50%). Epidermotropism and lymphocytic atypia were the most common pathologic features, found in 89% and 85%, respectively. Cerebriform nuclei were noted in 42%, and Pautrier microabscesses were seen in 16% of cases. A cytotoxic pattern was more commonly seen (67% vs 33%), and clonality was detected in 21% (3 of 14) of patients. All patients presented with early-stage disease and received skin-directed therapy (topical steroids, 73%; light therapy, 54%; or combination therapy, 35%). Conclusions: Pediatric patients with MF present in the first decade of life, with early-stage disease and unusual forms such as hypopigmented variant. Further patient enrolment will provide information regarding natural history, treatment response, and overall prognosis of pediatric cutaneous T-cell lymphoma (CTCL).

DNA restriction fragment length polymorphisms in the rDNA repeat unit of Entomophaga

A heterologous rDNA probe was used to detect restriction fragment length polymorphisms in Entomophaga rDNA sequences. Six Canadian strains of Entomophaga aulicae, isolated from the spruce bud worm or hemlock looper in Ontario or Newfoundland, showed no detectable rDNA variation at 10 different restriction enzyme loci: BamHI, DraI, EcoRI, EcoRV, HindIII, HinfI, MspI, PstI, RsaI, or TaqI. A total of 14 isolates of E. aulicae representative of several different geographic and host origins were compared at the DraI and HindIII rDNA loci and two different banding patterns were detected. Of these, 12 showed the same patterns and were designated E. aulicae type 1. The two members which differed were designated E. aulicae type 2. The variations in rDNA restriction sites did not appear to be geographically dependent. Entomophaga maimaiga, a recently reclassified species from the E. aulicae complex, displayed an rDNA banding pattern clearly distinguishable from the E. aulicae patterns with DraI, EcoRI, EcoRV, or HindIII. Members of the E. grylli species complex exhibited patterns which clearly differed from the patterns seen with either E. aulicae or E. maimaiga isolates. However, members of the E. grylli species complex appeared to be more heterogeneous than those in the E. aulicae complex. Among four E. grylli members, three different rDNA banding patterns were detected with either HindIII or DraI. These were designated as E. grylli type 1, type 2, and type 3. An undesignated Entomophaga isolate from a dipteran host displayed rDNA polymorphisms not previously noted in either the lepidopteran or orthopteran isolates. Our results suggest that RFLPs in rDNA are useful in the delineation of genera and species within the Entomophthorales, but may not be as useful at lower taxonomic levels. These and other RFLPs can however provide useful information regarding the epidemiology of Entomophaga epizootics.

Outbreak of acupuncture-associated cutaneous Mycobacterium abscessus infections.

Background: Cutaneous atypical mycobacterial infections have been increasingly described in association with cosmetic and alternative procedures. Objective: We report an outbreak of acupuncture-associated mycobacteriosis. Between April and December 2002, 32 patients developed cutaneous mycobacteriosis after visiting an acupuncture practice in Toronto, Canada. Results: Of 23 patients whose lesions were biopsied, 6 (26.1%) had culture-confirmed infection with Mycobacterium abscessus. These isolates were genetically indistinguishable by amplified fragment length polymorphism. The median incubation period was 1 month. Of 24 patients for whom clinical information was available, 23 (95.8%) had resolution of their infection. All patients developed residual scarring or hyperpigmentation. Conclusion: Nontuberculous mycobacteria should be recognized as an emerging, but preventable, cause of acupuncture-associated infections.

Psoriasis and the new biologic agents: interrupting a T-AP dance.

PSORIASIS IS AN IMMUNE-MEDIATED SKIN DISEASE in which chronic T-cell stimulation by antigen-presenting cells (APC) occurs in the skin. This interplay between the T-cell and APC has been likened to a “T-AP dance” where specific steps must occur in sequence to result in T-cell activation and the disease phenotype; otherwise T-cell anergy would occur. Several novel engineered proteins designed to block specific steps in immune activation (biologic agents) have demonstrated efficacy in the treatment of psoriasis. These agents include fusion proteins, monoclonal antibodies and recombinant cytokines. These medications act at specific steps during the T-AP dance either to inhibit T-cell activation, costimulation and subsequent proliferation of T-cells, lead to immune deviation or induce specific cytokine blockades. The potential increased selectivity for specific pathways in immune activation, clinical efficacy and relative safety of these new agents offers an alternative for the treatment of moderate to severe psoriasis.

Effect of a Single-Cycle Alternative Dosing Regimen for Rituximab for Recalcitrant Pemphigus: A Case Series of 9 Patients

BACKGROUND There is increasing evidence that a single cycle of rituximab (375 mg per square meter [corrected] of body surface area once weekly for 4 weeks) is efficacious in patients with severe pemphigus. The approved protocol in rheumatoid arthritis is 1 g on days 1 and 15. We report herein on the efficacy and safety of this latter protocol for rituximab in 9 patients with pemphigus. OBSERVATIONS Nine patients with recalcitrant pemphigus were treated with prednisone, immunosuppressive agents, and/or intravenous immunoglobulin. Rituximab, 1 g, was infused on days 1 and 15. Each patient was observed for a minimum of 6 months. Reepithelialization of at least 50% of the affected areas occurred in all patients within 16 weeks. Three of 6 patients (50%) discontinued intravenous immunoglobulin therapy. A significant decrease in the pemphigus severity score and the mean dosage of prednisone was observed at 3 and 6 months. Relapses were observed in 4 patients between 5 and 13 months after rituximab treatment; these patients completed a second cycle of rituximab. There were no serious adverse effects observed during the follow-up period. CONCLUSIONS A single cycle of rituximab, 1 g on days 1 and 15, is an effective treatment for pemphigus. Further studies are needed to determine the efficacy and safety of repeated treatment courses in patients who experience recurrences.

Sympatric occurrence of two Entomophaga aulicae (Zygomycetes: Entomophthorales) complex species attacking forest lepidoptera

Abstract Entomophthoralean fungi caused infections in sympatric larval populations of Lymantria dispar and Heterocampa guttivitta in New York and Vermont during 1989 and 1990. Gross morphology as well as restriction fragment length polymorphism and allozyme analyses determined that the Japanese fungus Entomophaga maimaiga was responsible for L. dispar mortality, while a different and otherwise unidentified member of the E. aulicae species complex was responsible for H. guttivitta mortality. Bioassays confirmed that the fungus infecting H. guttivitta was not E. maimaiga; the fungal isolate from H. guttivitta could not infect L. dispar larvae.

Pemphigus herpetiformis: a case series and review of the literature

Pemphigus herpetiformis (PH) is a rare subtype of pemphigus that presents challenges in diagnosis.

Cloned DNA probes distinguish endemic and exotic Entomophaga grylli fungal pathotype infections in grasshopper life stages

Entomophaga grylli is a fungal pathogen of grasshoppers and at least three pathotypes are recognized world‐wide. Pathotypes 1 and 2 are endemic to North America while the Australian pathotype 3 had been released into two field sites in North Dakota between 1989 and 1991. Grasshoppers were collected over the summer at the field sites in 1992 and assessed for pathotype infection by cloned DNA probe analysis. The three most predominant grasshopper species that were infected (Melanoplus sanguinipes, M. bivittatus and Camnula pellucida) were assessed for pathotype infection with respect to their life stages (nymphal instars and adult males and females). Pathotype 1 predominantly infected grasshoppers in the subfamilies Oedipodinae and Gomphocerinae and pathotype 2 predominantly infected grasshoppers in the subfamily Melanoplinae. Early‐instar M. sanguinipes and M. bivittatus had higher pathotype 2 infection frequencies, while late‐instar and adult C. pellucida had higher pathotype 1 infection frequencies. Cross‐infection by the pathotypes did occur in up to 3% of the individuals, on a per species basis, and primarily in later instar and adult grasshoppers. Pathotype 3 infections occurred in later instar and adults of the three grasshopper species. Infection of grasshoppers by E. grylli pathotypes is discussed with reference to the fungal life cycles.

Cost and Resource Use of Pemphigus and Pemphigoid Disorders Pre- and Post-Rituximab:

Background Rituximab (RTX) is increasingly used for the treatment of pemphigus and pemphigoid disorders. The high cost of RTX frequently limits its use and access. Objective To determine the health system resources and costs associated with RTX treatment of pemphigus and pemphigoid. Methods Health system resources and costs attributed to a convenience sample of 89 patients with either pemphigus or pemphigoid were identified, quantified, and valued 6 months prior to and following RTX initiation between May 2006 and August 2012. Overall cohort costs and costs per patient were calculated (2013 Can

Corticosteroid‐induced hyperglycemia is increased 10‐fold in patients with pemphigus

). Results The overall cohort cost for 6 months pre-RTX was