Factors associated with pruritic papular eruption of human immunodeficiency virus infection in the antiretroviral therapy era.

BACKGROUND: Pruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure. OBJECTIVES: To determine factors associated with PPE in HIV-infected persons receiving ART. METHODS: A case-control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥ 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration. RESULTS: Twenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA < 400 copies mL(-1) (96% vs. 85%, P = 0·31). The odds of having PPE increased fourfold with every log increase in viral load at ART initiation (P = 0·02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8(+) T-cell activation measured 6 and 12 months after ART commencement were not associated with PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8·3, P < 0·001] or PPE cases (OR 8·6, P = 0·01). CONCLUSIONS: Pruritic papular eruption in HIV-infected persons receiving ART for ≥ 15 months was associated with greater HIV viraemia at ART commencement, independent of CD4 count. Skin biopsies are important to distinguish between PPE and other itchy papular eruptions.

Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma.

BACKGROUND: A recent small series demonstrated perfect sensitivity and specificity utilizing immunostaining for PHLDA1, a marker of follicular stem cells, in the distinction of desmoplastic trichoepithelioma and morphoeiform basal cell carcinoma (BCC) in small biopsy specimens. OBJECTIVES: To assess this result more broadly. METHODS: We performed immunoperoxidase staining of BCCs (superficial n = 16, nodular n = 15, micronodular n = 15, infiltrative n = 17, morphoeiform n = 16, infundibulocystic n = 14) and trichoepitheliomas (conventional n = 19, desmoplastic n = 16) with PHLDA1. RESULTS: Morphoeiform BCCs typically lacked PHLDA1 staining (88% demonstrated no staining and 12% of cases had staining in < 25% of the tumour), while in contrast 74% of classical and 88% of desmoplastic trichoepitheliomas demonstrated strong PHLDA1 staining in over half of the tumour. However, micronodular BCCs demonstrated focal to diffuse positive staining in a third of the cases. CONCLUSIONS: Based upon our staining results, we discuss the biological significance of PHLDA1 expression and the limits in its diagnostic utility.

What genomics has taught me about melanocytic neoplasms.

Recent advances in the molecular biology of melanocytic neoplasms have enabled what were previously investigational tools to be used for more accurate diagnosis of melanocytic neoplasms. These include fluorescence in situ hybridization, comparative genomic hybridization, and sequencing. Correlation with conventional histopathology and immunohistochemistry has led to a better understanding of the classification of melanocytic neoplasms, as well as to the identification of new clinicopathologic entities. Herein are illustrated some pitfalls in the diagnosis of melanoma, as well as variants of Spitz's nevus that correlate with specific genomic aberrations such as gains of chromosome 11p and loss of the BAP-1 gene on chromosome 3p.

Nodular lesions arising in a large congenital melanocytic naevus in a newborn with eruptive disseminated Spitz naevi.

Congenital malignant melanoma within a pre-existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark-brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome-shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign proliferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi.

Celecoxib-induced Sweet's syndrome.

Sweet's syndrome and related neutrophilic dermatoses have been associated with a variety of medications. Celecoxib is a new cyclo-oxygenase-2 inhibitor recently approved for arthritis. We describe a 57-year-old man who experienced tender pustulopapular lesions on the dorsal aspects of the hands, neck, and legs 1 week after starting celecoxib. Histopathologic examination of the lesion showed a diffuse dermal neutrophilic infiltrate, edema of the papillary dermis, spongiform pustules, and no leukocytoclastic vasculitis. These findings were consistent with Sweet's syndrome. Without realizing a possible association, the patient rechallenged himself with a second course of the medication, which resulted in a rapid exacerbation of his lesions. After discontinuing the medication for the second time, the patient has had complete clearing of his lesions. To our knowledge, this is the first report of Sweet's syndrome associated with this new class of nonsteroidal anti-inflammatory drugs.

Anetoderma arising in cutaneous B-cell lymphoproliferative disease.

Anetoderma is circumscribed atrophy of the skin due to a localized deficiency in elastic tissue. It can follow inflammatory skin diseases of several types, and occasionally is present in the skin around neoplasms. There are a few reports of anetoderma in the lesional skin of cutaneous lymphoma. We report on two patients who presented with multiple lesions of anetoderma and who later proved to have low-grade cutaneous B-cell lymphomas. One patient (Patient 1) is a 39-year-old man and the other patient is a 26-year-old woman who is a renal transplant recipient (Patient 2). Some biopsy specimens from the anetodermic skin of Patient 1 appeared to show an urticarial reaction, although plasma cells were present. A large nodule showed lymphoid follicles surrounded by plasmacytoid lymphocytes, with loss of elastic tissue in the adjacent dermis. The plasmacytoid cells stained overwhelmingly for lambda light chain, and staining of the urticarial lesions from this patient also showed a marked majority of lambda positive cells. Immunoglobulin heavy chain gene (IgH) rearrangements showed a dominant clonal pattern in the nodular lesion. We classified the disease in Patient 1 as marginal zone lymphoma and the disease in Patient 2 as a post-transplant lymphoproliferative disorder. Because of the intimate association of anetoderma and cutaneous B-cell lymphoproliferative disorders in these two patients, it seems possible that anetoderma could result from either a local effect of the neoplastic cells or associated inflammatory cells, especially neutrophils as in Case 1. The infiltrates of Case 1 had many interstitial neutrophils and only a few clonal plasmacytoid lymphocytes, indicating that this presentation of B-cell lymphoma can be a diagnostic pitfall. Given these two cases and similar ones in the literature, biopsy of lesional skin in anetoderma should be performed to ensure that lymphomatous infiltrates are not present. Even if plasma cells are sparse, studies to detect clonality are appropriate. Cutaneous B-cell lymphoma can be added to the list of associations of elastolysis and cutaneous lymphoma, which includes granulomatous slack skin (T-cell lymphoma) and cutis laxa (myeloma).

Natural killer/natural killer-like T-cell lymphoma, CD56+, presenting in the skin: an increasingly recognized entity with an aggressive course.

PURPOSE: To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin. PATIENTS AND METHODS: This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters. RESULTS: The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P =.0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30- tumor cells (20 patients), who had a median survival of 9.6 months (P <.02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3epsilon, EBV, or multidrug resistance. CONCLUSION: NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.

Nephrogenic fibrosing dermopathy.

This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.

Detection of type 1 cytokines in discoid lupus erythematosus.

BACKGROUND: Although multiple studies suggest a dysregulated T-cell cytokine production in systemic lupus erythematosus, the cytokine profile in discoid lupus erythematosus (DLE) lesions is unknown. OBJECTIVES: To characterize the cytokine profile in DLE by immunohistochemical and molecular methods, and to investigate the role of cytokines in the pathogenesis of DLE. DESIGN: Patients were evaluated clinically, and biopsy specimens of lesional skin were examined by light microscopy. Reverse transcriptase-polymerase chain reaction and immunohistochemical analysis were performed on 11 biopsy specimens. We investigated the presence of interleukin (IL) 2, interferon gamma (IFN-gamma), IL-4, tumor necrosis factor alpha, (TNF-alpha), and IL-1beta messenger RNA (mRNA) in 8 biopsy specimens of DLE and compared it with 3 biopsy specimens of normal skin. SETTING: Academic referral research hospital. PATIENTS: Eight consecutive patients with a clinical and histologic diagnosis of DLE. RESULTS: Localized DLE was found in 7 patients and widespread in 1. During the 4 years of the investigation, none of the patients developed systemic lupus erythematosus. We found significantly elevated levels of IL-2 and IFN-gamma mRNA in all 8 biopsy specimens of DLE; in contrast, no transcripts of IL-2 or IFN-gamma were detected in 3 biopsy specimens of normal skin (P<.01). Similarly, elevated levels of TNF-alpha mRNA were detected in 8 DLE biopsy specimens, while no TNF-alpha mRNA was detected in 3 biopsy specimens of normal skin (P<.01). No IL-4 or IL-1 beta mRNA was detected in 8 biopsy specimens of DLE lesional skin and 3 biopsy specimens of normal patient skin. Immunohistochemical analysis showed increased staining for IL-2 and IFN-gamma receptors, while no detectable IL-4 receptor was found. No cytokine mRNA or cytokine receptor protein was detected in biopsy specimens of normal skin. CONCLUSIONS: These findings suggest that DLE is associated with type 1 cytokines characterized by the expression of IL-2 and IFN-gamma. Type 1 cytokines may be critical for induction, development, and maintenance of DLE.