J. Clark Huff

Erythema multiforme: Clinical, histopathologic, and immunologic study

In a prospective study of erythema multiforme, forty-two cases were selected with the use of defined criteria. In thirty-three cases (79%), the erythema multiforme occurred following a lesion of recurrent herpes simplex; in four cases (10%), it was related to administration of a sulfonamide drug. Herpes-associated erythema multiforme (HEM) was largely recurrent erythema multiforme minor and was characterized histopathologically by inflammatory changes, such as spongiosis and exocytosis, and by focal liquefaction degeneration of the basal cell zone of the epidermis. Sulfa-associated erythema multiforme (SEM) was a nonrecurrent illness with widespread cutaneous and mucosal damage associated with prominent histologic necrosis of epidermal cells. The deposition of C3 and fibrin along the dermoepidermal junction and the deposition of IgM, C3, and fibrin around dermal blood vessels by immunofluorescence microscopy were similar in both groups. Although HEM and SEM may have somewhat different clinical and histologic features, there is significant overlap in the pattern of tissue damage.

Immunogenetics of the Neonatal Lupus Syndrome

Abstract Infants with neonatal lupus erythematosus have congenital heart block, transient cutaneous lesions, or both. Mothers of these infants have SSA/Ro autoantibodies that are passed across the ...

Detection of a Herpes Simplex Viral Antigen in Skin Lesions of Erythema Multiforme

The commonest variety of erythema multiforme follows a lesion caused by a recurrent herpes simplex virus infection. In studying the immunopathogenesis of herpes-associated erythema multiforme, we examined skin lesions for the presence of a herpes simplex viral antigen by an indirect immunofluorescence test using a monoclonal antibody to a major type-common glycoprotein antigen, gB. Focal staining showed this antigen to be present in epidermal cells in 12 of 16 skin biopsy specimens. The staining was similar to, but less intense than, that seen in biopsy samples of lesions of recurrent herpes simplex virus infections. Similar findings were not seen in control skin biopsy specimens from lesions of other skin diseases; a control monoclonal stain also was negative in biopsy specimens. These findings suggest that the immune reaction and subsequent tissue damage of herpes-associated erythema multiforme are due to the presence of herpes antigens in the skin.

Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis

BACKGROUND Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which this virus may be present in the blood during a localized infection in otherwise healthy adults is unknown. OBJECTIVE The purpose of this study was to determine whether HSV may be detected in the peripheral blood during acute recurrent herpes labialis. METHODS Peripheral blood mononuclear cells (PBMCs) were obtained from otherwise healthy adults with recurrent herpes labialis, both during an acute episode and several weeks after the lesions had healed. The PBMCs were examined for the presence of HSV with the polymerase chain reaction (PCR) and viral culture. RESULTS By PCR, HSV DNA was detected in 7 of 34 specimens from an acute episode but in none of 24 specimens in the convalescent stage (p less than 0.004). PBMCs from seven donors, who were seronegative for HSV, were also negative for HSV by PCR. Viral cultures of 22 PBMC specimens were negative (including four specimens that were positive by PCR). CONCLUSION The presence of HSV DNA in the blood is a transient phenomenon limited to the period of active infection in a minority of patients with herpes labialis, although it may be important in the development of disseminated disease as well as in the pathogenesis of herpes-associated cutaneous processes such as erythema multiforme.

Misdiagnosis, Treatments, and Outcomes in the Immunobullous Diseases in Children

Abstract: As a group, the immunobullous diseases are very uncommon in childhood. We analyzed all cases of immunobullous diseases in individuals under age 18 years which we had evaluated at the University of Colorado and examined their age of onset, diagnostic difficulties, treatments, and outcomes. This was considered to be a representative North American population within a single referral area which contained a diverse ethnic population mixture. Further, we believe this study to be uniquely uniform in that all the patients were examined by us using the same diagnostic strategy and the immunofluorescent (IF) diagnostic tests were performed by the same individual (J. C. Huff) using uniform diagnostic criteria and consistent IF techniques.

Varicella-zoster virus infection of human mononuclear cells

Varicella-zoster virus (VZV) DNA was detected in mononuclear cells (MNC) of 7 humans with acute zoster 1-23 days after the onset of skin lesions. To further study the interaction of VZV with human MNC, cells obtained from seropositive normal donors were infected with VZV and analyzed for the presence of viral DNA and proteins. VZV-DNA was detected in T, B, and OKM 1 (monocyte-macrophage) positive cells, and virus-specific proteins were demonstrated by indirect immunofluorescence and immunoprecipitation. Hybridization studies revealed that VZV-DNA did not replicate in human MNC.

Acyclovir for recurrent erythema multiforme caused by herpes simplex

Herpes-associated erythema multiforme can be controlled by continuous suppressive treatment with oral acyclovir. Erythema multiforme is not prevented if oral acyclovir is administered after a herpes simplex recurrence is evident and it is of no value after erythema multiforme has occurred. There is some question whether continuous topical treatment with acyclovir to sites of recurrent herpes will sometimes prevent erythema multiforme. Erythema multiforme may be precipitated by orolabial and genital recurrences and by recurrences on skin of the buttocks and other sites. Some herpetic recurrences are associated with erythema multiforme and some are not and episodes of erythema multiforme are not always associated with clinical herpetic recurrences.

Examination of non‐involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes‐associated erythema multiforme

The association between infection with HSV and the subsequent, development of erythema multiforme is well established, although the role that the virus plays in the pathogenesis of this disorder is not known. HSV DNA has been detected in cutaneous lesions of herpes‐associated erythema multiforme (HAEM), and it has been suggested that the tissue damage seen in these lesions is virus‐specific. In the current, prospective study, we examined biopsies of lesional, non‐involved, and previously involved but healed skin, in addition lo specimens of peripheral blood, from patients with HAEM, for HSV DNA by using the polymerase chain reaction. HSV DNA was detected in lesional skin of 10 of 11 patients compared to 2 of 11 non‐involved skin biopsies obtained at the same time. I ISV was present in 4 of 6 blood specimens obtained during the acute episode. Five patients returned 3 months after the acute episode resolved for biopsies of previously involved skin. HSV was detected in 4 of these 5 biopsies. Thus, the presence of HSV DNA in the skin of pal inns with HAEM appears lo be predominantly in areas of clinical involvement; the virus remains in those cutaneous sites for up to 3 months without evidence of clinical disease; and HSV DNA may be detected in the peripheral blood cells during acute HAEM. Based on these findings, we suggest that the virus plays a role in lesion development, that the skin may function as a site of viral persistence, and that hemalogenous spread of viral DNA may bean important factor in the development of HAEM.

Transplantation of human basal cell carcinomas to athymic mice

Basal cell carcinomas (BCCs) obtained from 22 subjects undergoing microscopically controlled surgery were transplanted to 40 athymic (nude) mice. With no further immunosuppression of the mice, no tumor growth was noted in the first 14 attempts. When mice were further immunosuppressed with anti‐lymphocyte serum (ALS) injections and by splenectomy, successful tumor growth was achieved in 15 of 22 mice by a subcutaneous implantation technique and in 1 of 4 by a superficial grafting technique. Transplanted BCC retained the morphology and basement membrane proteins typical of human BCC. As determined by autoradiography, 3H‐thymidine was incorporated primarily in the peripheral palisaded cells of the transplanted tumor. Successful use of the athymic mouse model for study of human BCC requires use of mice further immunosuppressed by splenectomy and ALS, and the use of a subcutaneous implantation technique. With the use of this model, studies of the biology of human BCC may be possible.

Neonatal lupus syndrome in successive pregnancies

Two female siblings, born 15 months apart, developed neonatal lupus syndrome. Both had cutaneous lupus erythematosus (LE) lesions resolving with telangiectasis. Their cutaneous lesions were temporally related to transplacental passage of anti-SS-A (Ro) autoantibodies from their asymptomatic mother. Infants with this transient collagen vascular syndrome may have LE skin lesions, congenital heart block, and liver or hematologic abnormalities, and are possibly at risk for developing systemic lupus erythematosus (SLE) later in life. It is important to recognize that this syndrome may occur in successive pregnancies.