A role for NF-kappaB-dependent gene transactivation in sunburn.

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-kappaB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-kappaB-dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-kappaB cis element (NF-kappaB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-alpha, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-kappaB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-kappaB target genes, rather than from nonspecific changes associated with tissue damage.

Expression of transforming growth factor beta and transforming growth factor beta receptors on AIDS-associated Kaposi's sarcoma.

Several humoral growth factors may contribute to the development and growth of AIDS-associated Kaposi's sarcoma (KS). They are either provided by chronically activated cells of the immune system or in an autocrine/paracrine manner by the neoplastic cells themselves. Transforming growth factor beta(TGF-beta) may directly enhance the growth of KS cells and tumor matrix formation. To mediate a signal both TGF-beta receptors type I and type II (TbetaR-I and TbetaR-II) have to be expressed. We investigated the expression of TGF-beta, TGF-beta receptors types I and II, and endoglin, a nonsignaling-type TbetaR-III, by means of immunohistochemistry on skin biopsies from patients with AIDS-related KS. We found that the TGF-beta ligand was expressed by KS cells in 9 of 11 samples. TbetaR-II was strongly expressed in 10 of 12 samples, but none of the investigated tumor samples stained for TbetaR-I. Endoglin was weakly expressed on all KS lesions and stained the endothelium of tumor-associated vessels in 92% of the samples. These findings show that most KS lesions have the ability to produce TGF-beta and that KS cells maintain a high expression of TbetaR-II in the absence of TbetaR-I, which may allow KS to escape growth inhibitory effects of endocrine or paracrine TGF-beta.

Human immunodeficiency virus infection and the skin.

The skin is commonly affected in the course of human immunodeficiency virus (HIV) infection. In many cases, skin findings may be the earliest sign of HIV disease or acquired immunodeficiency syndrome. When cutaneous diseases occur in unusual settings, such as zoster in a young individual, are increased in severity or fail to respond to routine therapy, the possibility of underlying immunodeficiency should be suspected. Skin diseases in HIV-infected hosts include primary infections, such as those caused by herpes simplex virus and molluscum contagiosum, as well as secondary involvement of systemic diseases, such as cryptococcosis and histoplasmosis. Noninfectious inflammatory processes, such as seborrheic dermatitis and psoriasis, as well as neoplasms, such as Kaposi's sarcoma and basal cell carcinoma, may all be seen in these patients. We review a number of these diseases and discuss their treatment. Clinicians must be aware of the cutaneous manifestations of HIV infection so that the disease will be recognized at an earlier point in time and therapy with zidovudine and prophylactic antibiotics will be instituted where appropriate.

Clinical, histologic, microbiologic, and biochemical characterization of the causative agent of bacillary (epithelioid) angiomatosis: a rickettsial illness with features of bartonellosis.

It has been suggested that bacillary (epithelioid) angiomatosis (BEA) is a manifestation of cat scratch disease (CSD). Because of clinical similarity between this condition and the verruga peruana phase of bartonellosis, we sought to further characterize this disease as well as its causative agent and to compare it to bartonellosis. We isolated a small flagellated pleomorphic bacillus from skin lesions of two patients with BEA. Organisms were stained successfully with Warthin-Starry silver stains, but immunohistochemistry failed to demonstrate binding with a polyclonal antibody directed against the cat scratch bacillus. Whole cell fatty-acid gas chromatography performed on both BEA organisms and Bartonella bacilliformis demonstrated marked similarity between the two. Electron microscopy of BEA organisms in tissue and in suspension revealed features characteristic of a gram negative bacillus. Based on these findings, we propose that this unusual rickettsial infectious disease with vascular proliferation may represent an unusual variant of infection with a bartonella-like organism rather than a manifestation of cat scratch disease.

Cutaneous Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome.

Extrapulmonary infection with Pneumocystis carinii is an uncommon event in which the skin may be affected rarely. All cases heretofore described in immunocompromised hosts have involved the external auditory canal and mastoid areas. We describe two patients with acquired immunodeficiency syndrome and extrapulmonary cutaneous P carinii infection that involved the glabrous skin. The first was a 31-year-old white man seropositive for human immunodeficiency virus with prior episodes of P carinii pneumonia and infection with Mycobacterium avium-intracellulare evaluated for translucent papules on the skin with an appearance similar to molluscum contagiosum infection. Biopsy confirmed the diagnosis of cutaneous pneumocystosis. The second patient was a 36-year-old homosexual man with long-standing liver disease with a persistent cough, fever, and an abnormal chest roentgenogram. Cutaneous evaluation revealed a bluish macule on the sternal notch that on skin biopsy was diagnostic of cutaneous pneumocystosis. Treatment with intravenous pentamidine resulted in resolution of the pulmonary and cutaneous problems in both cases. Extrapulmonary P carinii infection may involve the skin at sites other than the external auditory canal and may have a nondescript appearance. Histologic findings are similar to those of pneumocystosis found elsewhere. Clinicians should be familiar with the nondescript nature of the eruption as skin biopsy may be helpful in establishing a diagnosis of systemic pneumocystosis.

An unusual presentation of secondary syphilis in a patient with human immunodeficiency virus infection. A case report and review of the literature.

BACKGROUND: Syphilis has been reported to assume unusual clinical appearances and to exhibit unusual courses in patients infected with the human immunodeficiency virus (HIV) type 1. We recently observed a distinct manifestation of syphilis in an HIV-infected patient with features not previously described. OBSERVATIONS: A 38-year-old HIV-seropositive homosexual man presented with fever, chills, malaise, and a cutaneous eruption consisting of indurated, shiny, erythematous plaques that were confluent on the face and scalp leading to alopecia and extreme tautness of the skin. Initial clinical diagnoses included lymphoreticular malignancy and infection. Although cultures yielded Staphylococcus aureus, a skin biopsy specimen was diagnostic of syphilis. CONCLUSIONS: This case demonstrates an unusual clinical manifestation of syphilis in a patient with HIV infection and emphasizes the importance of considering cutaneous secondary syphilis in the differential diagnosis of virtually any inflammatory cutaneous disorder in HIV-seropositive individuals.

Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia.

BACKGROUND AND DESIGN: Hepatitis C virus (HCV) infection is associated with mixed cryoglobulinemia, which can cause a vasculitis affecting various organs. To determine the prevalence of cutaneous vasculitis in patients infected with HCV, information concerning a series of 408 HCV antibody-positive outpatients was analyzed. Patients with a skin eruption were evaluated by a dermatologist for objective evidence of cutaneous vasculitis, and the sensitivity of cryoglobulins was compared with that of rheumatoid factor activity as a serologic marker of mixed cryoglobulinemia in these patients. RESULTS: Cutaneous vasculitis was identified in 10 of 408 HCV-infected patients (prevalence of at least 2%). The vasculitis was manifested as palpable purpura in eight patients, livedo reticularis in one patient, and urticaria in one patient. The skin eruption was a major presenting feature in each of the 10 patients and even led to the discovery of occult HCV infection in two patients. Histologic examination revealed leukocytoclastic vasculitis in six patients and necrotizing arteritis consistent with polyarteritis nodosa in two patients. All 10 patients had chronic active hepatitis and exhibited rheumatoid factor activity. Variable features attributable to mixed cryoglobulinemia included arthropathy, central nervous system abnormalities, and glomerular disease. Serum cryoglobulins were detected in only four patients. CONCLUSIONS: Practitioners should be alert to the possibility of HCV infection in patients presenting with palpable purpura, livedo reticularis, or urticaria, in which the underlying histologic features are those of leukocytoclastic vasculitis or necrotizing panarteritis. Positive serologic test results for HCV antibody and rheumatoid factor in such patients virtually confirm the diagnosis of HCV-induced mixed cryoglobulinemia.

A comparison of the efficacy and safety of Jessner's solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses.

BACKGROUND AND DESIGN: We compared the efficacy and safety of a medium-depth chemical peel with those of the standard regimen of topical fluorouracil in the treatment of widespread facial actinic keratoses (AK). Fifteen patients with severe facial actinic damage and similar numbers of AK on both sides of the face were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% fluorouracil cream for 3 weeks. Evaluations were conducted before treatment and at 1, 6, and 12 months after treatment. Visible AK were counted, random skin biopsies performed, adverse effects monitored, and patients questioned about preference and perception of efficacy. RESULTS: Both treatments reduced the number of visible AK by 75% and produced equivalent reductions in keratinocyte atypia, hyperkeratosis, parakeratosis, and inflammation, with no significant alteration of preexisting solar elastosis and telangiectasia. Except for erythema that lasted 3 months in one patient, no untoward side effects were observed with the chemical peel. The majority of patients preferred the peel over fluorouracil because of the single application and less morbidity. CONCLUSION: The medium-depth peel induced by Jessner's solution and 35% trichloroacetic acid is a useful alternative therapeutic option for widespread facial AK, particularly for poorly compliant patients, because it equals fluorouracil in efficacy while being superior in terms of the convenience of a single application with little associated morbidity.

Bacillary epithelioid angiomatosis occurring in an immunocompetent individual.

Within the last several years, a newly characterized condition known as bacillary epithelioid angiomatosis (BEA) has been described in a number of patients with human immunodeficiency virus (HIV) infection. All cases heretofore described have been seen in patients with the HIV infection. We recently evaluated a 37-year-old healthy man who had a localized form of BEA confirmed by biopsy, special strains, electron microscopy, and culture. We conclude that BEA as previously defined may occur in healthy, non-HIV-infected individuals.

Update on cutaneous manifestations of HIV infection.

The skin is affected in virtually all patients with HIV infection. Many articles and several books have been published that deal with these disorders for a number of reasons. First, cutaneous disease may serve as the initial or only problem that the patient suffers for much of the course of the HIV infection. Second, serious opportunistic infections may present for the first time in the skin, so that a skin lesion may be a harbinger of the patient's having a life-threatening illness. Third, skin disorders in these patients may appear unusual and hence may not be accurately diagnosed by clinical inspection alone. Furthermore, response to treatment may be poorer than expected. Thus, skin diseases in the HIV-infected patient are important and, in some cases, may be the most debilitating element of the patient's condition.

Actinic keratoses. Differential diagnosis and treatment.

Actinic keratoses are extremely common premalignant keratinocytic neoplastic lesions that develop primarily in fair-complexioned individuals during midlife or beyond. Genetic, occupational and other environmental factors predispose to the development of these lesions. Without treatment, a significant number may progress to fully developed neoplasms, especially squamous cell carcinoma, over a period of 20 to 50 years. The multistep theory of carcinogenesis is helpful in understanding the pathogenesis and progression of this important and highly prevalent lesion.

Noninfectious inflammatory skin diseases in HIV-infected individuals.

Noninfectious inflammatory skin diseases are often a persistent problem for patients with infection with the human immunodeficiency virus (HIV), and they present both diagnostic and therapeutic challenges for the dermatologist. Well-defined diseases such as granuloma annulare, reactions to insect bites, and leukocytoclastic vasculitis may be more severe in these individuals and may be refractory to therapy. More poorly defined conditions with psoriasiform and papular morphologies have also been described. A number of skin conditions, including pityriasis rubra pilaris, cutaneous T-cell lymphoma, and erythema elevatum diutinum, have recently been observed in the HIV-infected host. Because the dermatologist plays an important role in diagnosis and management of patients with HIV infection, it is important that he or she be well versed in the clinical manifestations and natural history of these conditions.

Update on the cutaneous manifestations of HIV infection. Clinical and pathologic features.

Skin is the most commonly affected organ in patients with HIV. As such, cutaneous manifestations of HIV infection have been the subject of intense scrutiny as well as the topic of many articles. A broad range of infectious and noninfectious skin lesions may develop during the course of the disease. This article discusses the clinical and pathological cutaneous manifestations of HIV infection.

Diagnosis and treatment of infectious diseases in HIV-infected hosts.

Treatment of infectious diseases in patients with HIV infection is of primary importance in patient care. Viral, bacterial, parasitic, and fungal pathogens all may affect these patients. It is essential that accurate diagnoses be made and appropriate therapy be administered as early as possible.

Delivery of dermatopathologic health care in the twenty-first century.

Dermatology and dermatopathology has experienced significant growth over the last century and continues to burgeon. Upheavals as a consequence of the advent of managed care have threatened both specialties, especially with regard to direct access and choice of consultant. The demand for dermatology and dermatopathology services continues to increase, and for patients to be served appropriately, these issues must be addressed.

Clinical features of dysplastic nevi.

The clinical features of 100 dysplastic nevi were tabulated. Although certain characteristics were present in most or all of these melanocytic nevi, there was a marked heterogeneity of other clinical features. The preponderant type of large (greater than or equal to 8 mm) melanocytic nevus in patients with classic dysplastic nevi is a papule or plaque with the following characteristics: multicoloration (various shades of tans, browns, reds, or black); slightly raised height for its broad diameter; mamillated surface; and lack of hypertrichosis. An atlas illustrates some of the clinical varieties of melanocytic nevi in this syndrome.

Mucocutaneous neoplasms in patients with human immunodeficiency virus infection.

Neoplastic disorders of the skin are commonly encountered in patients with human immunodeficiency virus infection. As patients survive longer, they are at ever increased risk to acquire one of a number of different malignant neoplasms of the skin. These may be of many different types including epithelial, lymphoreticular, vascular, smooth muscle, and melanocytic. Because of the immunocompromised status of these patients, many of these disorders behave in more aggressive fashions and require more aggressive treatment.

Biopsy technique for pigmented lesions.

The biopsy technique that should be used when sampling a pigmented lesion may not always be readily apparent. The final arbiter is whether the specimen that will be generated will be representative of the entire process so that an accurate and complete diagnosis will be able to be rendered. In some cases, melanoma may not be clinically suspected so that it is essential that any biopsy that is performed will detect these lesions.

Cutaneous malignant melanoma: classification and clinical diagnosis.

Cutaneous malignant melanoma (MM) is a treacherous disease which carries high mortality rates. However, when diagnosed early it is wholly curable. The incidence of MM is rising steadily. The most important clinical signs include the appearance of a newly acquired pigmented lesion or change in a preexisting one. Melanoma has been classified into subtypes which include melanoma in situ, lentigo maligna melanoma, nodular melanoma, acral lentiginous melanoma, desmoplastic melanoma, superficial spreading melanoma, and mucosal melanomas. Although these overlap, there are characteristic clinical features of each that are generally recognizable. Evaluation of pigmented lesions requires correlation of clinical findings with risk factors, family history and histology. A representative skin biopsy should be performed on any lesion suspected of being MM, even if the possibility is remote.