Gibson, Lawrence E.

AbstractIn this review, we summarize the recent literature and use case examples to reach diagnostic criteria for the diagnosis of immunoglobulin G4 (IgG4)‐related diseases that may be of relevance to the practicing dermatologist.

BackgroundComplications from graft‐vs.‐host disease (GVHD), a major contributor to morbidity and mortality following hematopoietic cell transplantation, may be mitigated by early diagnosis and intervention. However, differentiation between acute cutaneous GVHD and other common skin eruptions that develop in the post‐transplantation period, such as drug hypersensitivity reaction, can be challenging clinically and microscopically. Because recent evidence indicates that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis, we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous GVHD.MethodsWe studied 12 skin specimens of patients with grades I–II cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with vacuolar interface changes on biopsy.ResultsNo differences were seen between the two groups with regards to density or distribution of CD123 expression. Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and fewer dermal eosinophils (P = 0.03) compared to those representing drug hypersensitivity reaction.ConclusionsWe conclude that CD123 does not appear to be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful correlation between clinical findings and features with microscopy remains the cornerstone of accurate diagnosis of acute cutaneous GVHD.

ABSTRACT A 65-year-old male with known hypertension and hypercholesterolemia sought medical attention because of a 3-month history of skin swelling on his upper back. Histopathology and molecular techniques were employed and identified an organism in the Onchocerca genus. This represents a very uncommon example of cutaneous infection by a zoonotic Onchocerca species.

BackgroundHenoch‐Schönlein purpura (HSP) is a vasculitis that can affect the skin and kidneys. It is characterized by immunoglobulin (Ig) A‐predominant deposition in small blood vessels. To our knowledge, there has been no comparison of direct immunofluorescence (DIF) findings in skin and kidney biopsy specimens.MethodsWe retrospectively studied 21 adults with HSP who had IgA deposition in the skin and kidneys. The skin and kidney DIF findings were compared and tested for an association with the progression of renal disease.ResultsMean age of the patients was 51.4 years. Follow‐up data were available for 19 patients, of whom 5 had progression to chronic kidney disease or renal failure. Concordance between DIF findings on skin and renal biopsies was 100% for IgA, 80% for C3, 80% for IgG, 71% for IgM and 53% for fibrinogen. A worse renal outcome was associated with renal IgG deposition (p = 0.04). A trend for worse renal outcome was found with renal fibrinogen and skin IgM deposition (p = 0.10 and 0.14, respectively).ConclusionsIn this retrospective study of adult HSP, the concordance between DIF findings in skin and kidney specimens was low‐moderate. Further study is required to elucidate the mechanisms responsible for these differences in Ig deposition.

AbstractObjectivesWhole‐slide imaging with virtual microscopy is increasingly used as a tool in resident education and training, board certification and maintenance of certification examinations, and diagnostic evaluation. The objective of this study was to determine attitudes toward virtual microscopy compared with traditional glass slide microscopy during a continuing medical education dermatopathology workshop.MethodsTwenty‐three board‐certified, practicing or retired dermatopathologists were given 26 “advanced” cases to review using both virtual microscopy and traditional glass slides. Diagnostic accuracy was not assessed because of the complexity of the cases. Participants were surveyed on: (i) their previous experience with digital imaging; (ii) the quality, ease of use, and speed of slide review; and (iii) overall attitudes toward digital and traditional review.ResultsEqual proportions of participants did and did not have prior experience with digital imaging of histopathologic specimens. Most participants preferred to use both virtual microscopy and traditional microscopy together. The quality of glass slides was rated as better than that of digital images, but virtual microscopy achieved higher ratings for ease of navigation and overall satisfaction.ConclusionsVirtual microscopy is a useful tool for dermatopathology workshops. Specifically, dermatopathologists with and without prior digital slide review experience responded favorably to viewing slides on a computer monitor. Overall satisfaction was high, and the majority of participants indicated that they would use virtual microscopy in the future. These results show a trend toward the acceptance of digital slide review, which supports the inevitable expansion of this practice in an increasingly digitized world.

AbstractBackgroundThe term pharmacogenetics is used to describe an evolving field that aims to understand the relationship between individual variations in genetic sequence and differences in the therapeutic and toxic response to medications. The promise of pharmacogenetics is empowerment of clinicians with information that will enable them to personalize drug therapy – to prescribe the right medication at the right dose for each patient, while minimizing adverse effects. Despite dramatic advances, wide application of pharmacogenetics to clinical practice has been slow for a number of reasons, including lack of evidence‐based therapeutic guidelines as well as ethical concerns and cost.MethodsTo illustrate applications to dermatology practice, we present three clinical scenarios that serve as a springboard for discussion of the principles of pharmacogenetics and how they can be used to guide treatment with azathioprine, 5‐fluorouracil, and trastuzumab.ConclusionThe therapeutic and toxic effects of a given medication ultimately depend on its combined pharmacokinetic, pharmacodynamic, and pharmacogenetic properties in a given individual. Pharmacodynamic properties of individual medications must be correlated with single nucleotide polymorphisms. Test recommendations and standardization of therapy for specific disorders can then be established.

Generalized eruptive histiocytosis, described in 1963 by Winklemann and Muller, is a reactive, self‐healing form of non‐Langerhans histiocytosis. Rare cases of atypical generalized eruptive histiocytosis have been reported in patients with hematopoietic malignancy, but the biological relationship between the two disorders is not known. We report an 84‐year‐old man with chronic myelomonocytic leukemia who presented with coalescing erythematous papules and plaques on the posterior neck, ear and lower lip, followed by development of blast crisis. Skin biopsy revealed a thick band‐like dermal infiltrate of cells that exhibited morphologic features of macrophages or histiocytes and prominent elastolytic phagocytosis. These cells demonstrated a mature immunophenotype, expressing CD14 and CD68, with partial expression of CD13 but not CD1a, CD43, CD56, CD123, Langerin, or S‐100 protein. Karyotype and fluorescence in situ hybridization analyses showed loss of the Y chromosome in bone marrow and skin specimens, providing evidence of a clonal relationship between the cutaneous eruption and the underlying chronic myelomonocytic leukemia. The presence of the same clone in skin and bone marrow specimens from our patient supports the possibility that atypical generalized eruptive histiocytosis is a marker for underlying hematopoietic malignancy. Discovery of additional cases may shed further light on the pathogenesis of this rare entity.