Refining criteria for diagnosis of cutaneous infections caused by herpes viruses through correlation of morphology with molecular pathology.

BACKGROUND: Infections of the skin by herpes viruses do not always present themselves in typical fashion. Early diagnosis, however, is crucial for appropriate treatment. Polymerase chain reaction (PCR) allows diagnosis and differential diagnosis of herpes virus infections, but the method is not yet available in large parts of the world, where diagnosis is made based on morphology alone. AIM: To refine criteria for the diagnosis of herpes virus infections of the skin by way of correlation of clinical and histopathologic findings with results of PCR studies. METHODS: We studied 75 clinically diagnosed patients of "zoster," "varicella," and "herpes simplex", to correlate clinical and histopathological findings with results of PCR studies on paraffin embedded biopsy specimens. RESULTS: Clinical suspicion of infection by herpes viruses was confirmed by histopathology in 37% of the cases and by PCR studies in 65% of the cases. Zoster was frequently misdiagnosed as infection with herpes simplex viruses (30%). When diagnostic signs of herpes virus infection were encountered histopathologically, PCR confirmed the diagnosis in 94%. By way of correlation with results of PCR studies, initial lesions of herpes virus infections could be identified to have a distinctive histopathological pattern. Herpetic folliculitis appeared to be a rather common finding in zoster, it occurring in 28% of the cases. CONCLUSION: We conclude that correlation of clinical and histopathological features with results of PCR studies on one and the same paraffin embedded specimen permits identification of characteristic morphologic patterns and helps to refine criteria for diagnosis both clinically and histopathologically.

Herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive!

Infections of the skin by herpesviruses do not always present themselves in typical fashion. Conventional microscopy is used routinely to confirm infection by herpesviruses, but sometimes typical signs such as multinucleated epithelial cells or "ghosts" of them are not encountered in a specimen (so-called herpes incognito). We studied 35 patients in whom infection with herpesviruses was differentially diagnosed clinically but in whom a biopsy specimen had been taken for confirmation. Only those patients in whom histopathologic findings had been interpreted as being "not diagnostic" of herpesvirus infection by 2 independent dermatopathologists were included. Clinical and histopathologic findings were correlated with results from polymerase chain reaction studies on formalin-fixed paraffin-embedded tissue. Polymerase chain reaction revealed herpesvirus-specific DNA in 12 of 35 specimens, 10 being varicella zoster virus (VZV) positive, 1 herpes simplex virus (HSV)-2 positive, and 1 HSV-1 positive. Ten of these 12 cases presented themselves in very similar fashion (8 VZV, 1 HSV-1, 1 HSV-2). All lesions were macular or papular and typified mostly by dense perivascular and sparse interstitial superficial and deep infiltrates of lymphocytes, sometimes assuming a patchy lichenoid pattern. Infiltrates were prominent in and around adnexal structures, often peppering follicles, sebaceous glands, and eccrine glands. Lymphocytes were also found in the lower part of the epidermis accompanied by a combination of spongiosis and vacuolar alteration. The papillary dermis was often edematous; extravasated erythrocytes in variable numbers were a common finding. Lymphocytes sometimes had large and polygonal nuclei. Neutrophils and nuclear dust were present occasionally; eosinophils were rare. We conclude that herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive.