Heteroduplex analysis of T-cell receptor gamma gene rearrangement as an adjuvant diagnostic tool in skin biopsies for erythroderma

Background: Erythroderma, defined as red skin covering most of the body sur face often accompanied or followed by exfoliation, is the clinical manifest ation of at least six different underlying etiologies with allergic or irri tant contact dermatitis, atopic/asteotic dermatitis, pityriasis rubra pilar is (PRP), psoriasis, and seborrheic dermatitis accounting for the majority of cases. Approximately 10% of cases are due to adverse drug reactions with roughly another 10% due to cutaneous T-cell lymphoma (CTCL), predominantly mycosis fungoides, or leukemia. It is clear from multiple studies that the clinical diagnosis of the underlying entity is often difficult, as these d iseases can present in a very similar fashion. A skin biopsy is usually emp loyed in this setting as a diagnostic tool. However, the histopathologic di agnosis of the underlying cause is complicated by the subtlety of the disti nguishing histologic features. In this situation, an ancillary technique de monstrating the presence of a monoclonal T-cell proliferation could help to rule in or out CTCL in cases that clinically and histopathologically do no t allow a definitive diagnosis. Methods: We retrospectively studied 25 biopsies from sixteen patients who p resented to the Stanford Dermatology Clinic with erythroderma. We examined the specimens morphologically and analyzed the gamma chain of the T-cell re ceptor (TCR-gamma) by polymerase chain reaction (PCR) followed by heterodup lex analysis for clonality. We then correlated the results of our PCR and h eteroduplex analyses with the patients' clinical outcomes. Results: Four biopsies, from three patients, contained clonal TCR-gamma rea rrangements; the four biopsies, ail of which were equivocal histologically, correlated to diagnoses of mycosis fungoides (MF) or Sezary syndrome (SS). Twenty-one biopsies contained polyclonal T-cell populations. Eighteen of t hese biopsies represent patients with inflammatory dermatoses. Three of the se biopsies, all of which were taken from a single patient, correlate to a diagnosis of MF. Conclusion: TCR-gamma PCR heteroduplex analysis seems to represent an impor tant adjuvant diagnostic tool that, used in conjunction with histopathology and clinical history, could help to clarify the underlying etiology of ery throderma.