Clay J. Cockerell

EPITHELIOID ANGIOMATOSIS: A DISTINCT VASCULAR DISORDER IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME OR AIDS-RELATED COMPLEX

Unusual cutaneous vascular neoplasms distinct from Kaposis sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor VIII antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour.

Decubitus ulcers: A review of the literature

Decubitus ulcers are a worldwide health care concern affecting tens of thousands of patients and costing over a billion dollars a year. Susceptibility to pressure ulcers comes from a combination of external factors (pressure, friction, shear force, and moisture), and internal factors (e.g. fever, malnutrition, anaemia, and endothelial dysfunction). Often, enough damage is done to create the basis for a decubitus ulcer after as little as 2 h of immobility, a situation which may be difficult to avoid if the patient must undergo prolonged surgery or remain bedridden. Damage owing to pressure may also occur hours before the patient receives medical attention, especially if the patient falls or becomes immobilized owing to a vascular event. Several classification systems for decubitus ulcers have been described, based on where injury first occurs. The histologic progression of decubitus ulcers is a dynamic process involving several stages, each having characteristic histologic features. A team‐focused approach integrating all aspects of care, including pressure relief, infection control, nutrition, and surgery, may improve healing rates. With accurate risk assessment and preventative care, we can hope to minimize complications and mortality owing to decubitus ulcers.

A role for NF-κB–dependent gene transactivation in sunburn

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB 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-κB-dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, 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-κB 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-κB target genes, rather than from nonspecific changes associated with tissue damage.

Bacillary Angiomatosis and Bacillary Splenitis in Immunocompetent Adults

Bacillary angiomatosis and parenchymal bacillary peliosis are recently described vascular disorders associated with infection by Rochalimaea henselae and Rochalimaea quintana, which occur in patients with either human immunodeficiency virus (HIV) infection or drug-induced immune suppression [1-5]. In addition, R. henselae and R. quintana (also the agent of trench fever) are both members of the family Rickettsiaceae [1, 4, 5], and infections due to Rochalimaea species have been associated with exposure both to cats [2] and to arthropod vectors [1, 5]. We describe five patients with cutaneous bacillary angiomatosis or bacillary splenitis without evidence of HIV infection who were determined to be immunocompetent after immunologic evaluation. In three patients with both cat and cat flea exposures, infection by R. henselae was confirmed by amplification and sequencing of 16S rDNA from an infected tissue specimen. Methods Four patients with characteristic vascular lesions of cutaneous bacillary angiomatosis [1, 3] were examined. Patient 2, who lacked vascular lesions, had a 2-week history of left-sided abdominal pain, shortness of breath, low-grade fever, nausea, diarrhea, and weight loss of 3.5 kg. Results of laboratory studies included hematocrit, 0.21 (2 months before it had been 0.34); lactate dehydrogenase, 1170 U/L; total bilirubin, 53 mol/L (3.1 mg/dL); conjugated bilirubin, 24 mol/L (1.4 mg/dL); and mildly elevated hepatic transaminases and alkaline phosphatase. A computed axial tomography scan of the abdomen showed a normal liver and hypersplenism with a 4-cm2 area of focal low attenuation. The patient underwent emergency splenectomy for impending rupture. The 1100-g spleen revealed a 4.5-cm3 mottled area consistent with infarction and two 0.6-cm3 tan nodules beneath the capsular surface. Results of routine bacterial cultures were negative. In June 1991, all five patients had blood drawn for HIV culture, serologic analysis, and polymerase chain reaction studies using techniques described previously [6, 7]. In August 1991, all patients had blood drawn for immunologic evaluation, including quantitative immunoglobulins, complement, lymphocyte subset percentages, neutrophil oxidative burst [8, 9], T-lymphocyte activation studies to phytohemagglutinin, and B-lymphocyte activation studies to pokeweed mitogen [10, 11]. After their blood was drawn, patients had skin test antigens to purified protein derivative, mumps, Trichophyton, and Candida albicans placed and read at 48 hours. The diagnosis of cutaneous bacillary angiomatosis was established using defined histopathologic criteria [3]. Bacterial DNA present in the infected tissue specimen was extracted from either frozen skin biopsy tissue (Patient 4) or from sections of formalin-fixed, paraffin-embedded biopsy specimens [1, 12]. Insufficient tissue was available from Patients 1 and 3. Extracted DNA was amplified by polymerase chain reaction using primers p24E and p12B [1, 12]. Control tissues were simultaneously extracted and amplified [1]. Amplified 16S rDNA products from Patients 2, 4, and 5 were sequenced as described previously [1]. Results Only Patient 2 had a well-documented antecedent chronic illnesshereditary spherocytosis and noninsulin-dependent diabetes mellitusand no patient was receiving immunosuppressive drugs (Table 1). Idiopathic hemochromatosis was diagnosed concomitantly with bacillary angiomatosis in Patient 3. All patients responded to oral antimicrobial therapy of 4 to 6 weeks duration. Histologic examination of skin biopsy specimens from Patients 1, 3, 4, and 5 were diagnostic of bacillary angiomatosis; splenic tissue from Patient 2 showed necrotizing splenitis with fibromyxoid changes, degenerating neutrophils, and mononuclear cells in the absence of both vascular proliferation and granuloma formation. Specimens from all patients showed many bacilli on both Warthin-Starry staining and electron microscopic examination. Table 1. Characteristics of Immunocompetent Patients with Bacillary Angiomatosis and Bacillary Splenitis Amplification of the DNA extracted from infected tissue from Patients 2, 4, and 5 produced a 16S rDNA fragment of approximately 300 base pairs. The amplified DNA fragment from tissue of Patients 2 and 4 is shown in Figure 1. The sequence of this 16S rDNA fragment from Patients 2, 4, and 5 was identical to that of R. henselae [4, 12]. Figure 1. Amplification of Rochalimaea DNA. Rochalimaea henselae R. henselae Discussion We evaluated four patients with cutaneous bacillary angiomatosis and one with bacillary splenitis and found no evidence of HIV infection using a combination of sensitive HIV antibody and antigen assays, as well as viral culture and polymerase chain reaction techniques. In addition, both cellular and humoral immunity were evaluated and no abnormality was found. Because host defense mechanisms against Rochalimaea species are not well understood, defects may have been undetected by our methods. Two patients had underlying illnesses that may be associated with altered immune function, but no consistent immune defect has been associated with these conditions [13-15]. The histopathologic findings were diagnostic for bacillary angiomatosis in all four patients with cutaneous disease; tissue from Patient 2 showed necrotizing splenitis with characteristic bacillary organisms [3, 12]. Amplification and sequencing of rDNA from tissue of Patients 2, 4, and 5 confirmed that the infecting organism was R. henselae. Although we cannot speciate the bacilli seen in abundance with the Warthin-Starry stains of Patients 1 and 3, the histopathologic changes met all criteria for the diagnosis of cutaneous bacillary angiomatosis [3], a disease associated with R. henselae and R. quintana [1]. Bacillary splenitis in the absence of peliosis appears to be another manifestation of R. henselae infection. A clinical spectrum of R. henselae infection may exist, beginning with fever and bacteremia, progressing to bacillary splenitis and finally to bacillary peliosis. Differences in host immune function also may play a role in disease progression. The diagnosis of cutaneous bacillary angiomatosis and bacillary splenitis should be pursued in the immunocompetent patient when clinical or histopathologic features are suggestive. On the basis of these five patients, we recommend treatment with erythromycin or doxycycline for at least 6 weeks when the diagnosis is confirmed.

Melanoma awareness and self-examination practices: Results of a United States survey

BACKGROUND Skin cancers are common and there has been a dramatic increase in their incidence, particularly melanoma. However, little is known about awareness of melanoma and early detection practices in the general U.S. population. OBJECTIVE In 1995, the American Academy of Dermatology increased their efforts to promote awareness of melanoma. This study was conducted to document current knowledge of melanoma and self-examination practices. METHODS In February 1995, a telephone survey was conducted in a nationally representative sample of 1001 persons at least 18 years of age (3% margin of error) that included questions on knowledge, attitudes, and practices regarding early detection of melanoma. RESULTS Almost 42% of those surveyed were unaware of melanoma, and only 26% of those who were aware could identify its specific signs. Most recognized at least one common risk factor for melanoma (e.g., sun exposure, fair skin). However, many did not distinguish melanoma from other skin cancers in terms of risk factors, signs of early disease, and body site distribution. The lowest measures of melanoma knowledge and attitudes were found among those who are male, nonwhite, and parents, and those with the lowest level of education and income. More than half (54%) did not conduct a self-examination. This practice was most frequently reported by women, white persons, and the elderly, as well as those with a greater knowledge of melanoma. CONCLUSION Our research documents deficiencies in knowledge and practices related to early detection of melanoma in the general U.S. population and supports the need for public education about melanoma.

Bacillary angiomatosis: a newly characterized, pseudoneoplastic, infectious, cutaneous vascular disorder

Bacillary angiomatosis (also called epithelioid angiomatosis) is a newly recognized disease most often characterized by a cutaneous infection with reddish papules of vascular origin. It is caused by a weakly reactive gram-negative bacillus, which can be easily demonstrated in tissue sections with the Warthin-Starry stain. Bacillary angiomatosis usually responds readily to treatment with oral erythromycin, 250 to 500 mg, taken four times a day for 2 weeks to 1 month. Because the skin is the most common site of involvement, it is important that the dermatologist recognize this unusual condition. It is essential that treatment be started as soon as possible because deaths may result from visceral and mucosal involvement. The clinical, histologic, and microbiologic aspects of bacillary angiomatosis are discussed and depicted in detail and speculations regarding the pathogenesis are rendered.

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.

Topical and intralesional cidofovir: A review of pharmacology and therapeutic effects

BACKGROUND Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or intralesionally in several virally induced cutaneous diseases. OBJECTIVE Our purpose was to review the usefulness of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir-resistant strains), Kaposis sarcoma-associated herpesvirus, and molluscum contagiosum. METHODS We performed a review of recent literature. RESULTS Cidofovir is a potent topical intralesional antiviral agent with activity against several DNA viruses that cause cutaneous disease. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. CONCLUSION The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in a limited number of patients including those infected with HIV. Although larger studies will be necessary to determine the specific function that topical cidofovir will have in the treatment of cutaneous diseases caused by DNA viruses, the drug offers significant promise.

Incipient intraepidermal cutaneous squamous cell carcinoma: a proposal for reclassifying and grading solar (actinic) keratoses.

Actinic keratoses (AKs) are primarily induced by ultraviolet (UV) radiation and are often identified as premalignant lesions. In our opinion, AKs are proliferations of transformed, neoplastic keratinocytes confined to the epidermis that may eventually extend into the dermis, at which point they are termed squamous cell carcinoma (SCC). In contrast to AKs, SCCs have the potential to metastasize and kill. This process is analogous to that of evolving carcinoma of the uterine cervix that has been termed cervical intraepithelial neoplasia (CIN), a time-tested and reliable classification that provides clinicians with accurate information on which to base treatment decisions regarding cervical neoplasms following biopsy testing. A similar classification scheme could provide guidance to clinicians for the diagnosis and treatment of evolving SCC of the skin and as such, we propose a similar classification using the terminology keratinocytic intraepidermal neoplasia (KIN). This system is more reflective of the histology and natural history of SCC and eliminates ambiguity in the terminology of lesions currently referred to as AKs. The KIN classification defines features by which individual specimens can be objectively graded and specific treatment recommendations are made based on the grade of the lesion. We propose that the term keratinocytic intraepidermal neoplasia (KIN) be used to define and describe evolving SCC of the skin and that the term actinic (solar) keratosis be eliminated.

Sentinel lymph node biopsy as an adjunct to management of histologically difficult to diagnose melanocytic lesions: a proposal.

There is a significant subset of primary cutaneous melanocytic neoplasms that are difficult to diagnose with the use of routine light microscopy. The currently recommended approach in assessing such lesions is to make a histopathologic diagnosis that reflects some uncertainty and then to recommend complete surgical excision. While adequate in many cases, the excision that might be recommended for such a lesion if malignant would be mutilating in many others. To increase the sensitivity of diagnosis and to provide potentially useful prognostic information, we propose that sentinel lymphadenectomy be considered in patients with melanocytic neoplasms of uncertain behavior that are 1.0 mm or more in thickness.