Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.

BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.

Simple sample processing enhances malaria rapid diagnostic test performance.

Lateral flow immunochromatographic rapid diagnostic tests (RDTs) are the primary form of medical diagnostic used for malaria in underdeveloped nations. Unfortunately, many of these tests do not detect asymptomatic malaria carriers. In order for eradication of the disease to be achieved, this problem must be solved. In this study, we demonstrate enhancement in the performance of six RDT brands when a simple sample-processing step is added to the front of the diagnostic process. Greater than a 4-fold RDT signal enhancement was observed as a result of the sample processing step. This lowered the limit of detection for RDT brands to submicroscopic parasitemias. For the best performing RDTs the limits of detection were found to be as low as 3 parasites per µL. Finally, through individual donor samples, the correlations between donor source, WHO panel detection scores and RDT signal intensities were explored.

Coping as a mediator of stress and psychotic-like experiences.

BACKGROUND: There is evidence that individuals along the whole psychosis continuum have increased responsiveness to stress; however, coping responses to stressors have not been extensively explored in subthreshold psychotic symptoms. METHODS: In 454 undergraduates, psychotic-like experiences (PLEs) were evaluated using the positive items of the Prodromal Questionnaire. Perceived stress and traumatic life events were assessed using the Life Events Checklist and Perceived Stress Scale, and coping was measured using the Brief COPE. We also examined whether different coping styles mediated the relationship between perceived stress and PLEs, as well as whether different coping styles mediated the relationship between traumatic life events and PLEs. RESULTS: Both number of traumatic life events and current level of perceived stress were significantly associated with PLEs. These relationships were both mediated by higher levels of maladaptive coping. CONCLUSIONS: Results have the potential to inform treatment strategies, as well as inform targets for exploration in longitudinal studies of those at risk for psychosis.

Negative effects of oral fatty acid supplementation on sweat chloride in cystic fibrosis.

Essential fatty acid supplementation with oral safflower oil (1 gm/kg/day) to 11 cystic fibrosis patients (aged 6 months to 14 years) for one year produced no significant change in sweat chloride concentration (mEq/liter) or sweat rate (gm/min/m2), Addition of vitamin E (10 mg/kg/day) to the safflower oil had no effect on sweat chloride concentration or rate compared to placebo. No clinical improvement could be detected compared to a control group. These results do not support previous reports of the effects of fatty acid supplementation on sweat electrolyte concentrations in cystic fibrosis.

Cooperative study comparing three methods of performing sweat tests to diagnose cystic fibrosis.

Directors of cystic fibrosis centers in the United States have noted an increasing number of patients with histories of either false-positive or false-negative sweat tests. These inaccuracies were attributed to the use of rapid test methods which avoided actually weighing the sweat collected. These rapid tests have inherent difficulties which, theoretically at least, could lead to mistaken diagnoses. To evaluate methods of performing the sweat test, the National Cystic Fibrosis Foundation organized a combined study comparing the older Quantitative pilocarpine iontophoretic test (QPIT) method of performing the test with two newer and more rapid methods, the Orion skin electrode, and the Medtherm conductivity apparatus. Five cystic fibrosis centers participated in the study. Although two centers obtained considerably more accurate results with the Orion and the Medtherm than did the other three centers, the combined results of the study indicate that these procedures can be considered to be little more than screening tests.

Cutaneous vasculitis: approach to diagnosis and systemic associations.

The starting point in the evaluation of vasculitis is the clinical examination. The character and location of the primary lesions determine the type of biopsy specimens and additional tests needed to classify vasculitis. The most common causes of cutaneous vasculitis are drug reactions, infectious diseases, reactions to inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease, or association with malignant disease, especially lymphoproliferative disorders. Direct immunofluorescent techniques and leukocyte monoclonal antibody studies are useful for the diagnosis of selected cases of vasculitis. The clinical and histopathologic data help delineate an approach for further investigation of potentially associated systemic disorders or underlying causes. Although some cases of cutaneous vasculitis are not associated with systemic disorders, this possibility should never be assumed but considered only as a diagnosis of exclusion after careful examination of each patient.

Mucosal, genital, and unusual clinical variants of melanoma.

To demonstrate the need for a through cutaneous and mucosal examination, we discuss and illustrate the spectrum of mucosal melanomas and unusual clinical variants of melanoma. Although cutaneous areas exposed to sunlight are most vulnerable, melanomas can occur in any site on the skin or mucous membranes. Pigmented nevi as well as mucosal and labial melanotic macules are lesions that simulate oral mucosal melanomas but are not associated with such a poor prognosis. In contrast, the 5-year survival rate for patients with malignant melanomas of the oral mucosa is only 5%. Similarly, the prognosis is poor for patients who have malignant melanomas of the vulva, vagina, male genitalia, or anorectal area; most patients with such lesions are 50 years of age or older. Subungual and plantar areas are common sites of malignant melanomas, and involvement of the eyelid margin portends a poor prognosis. Other rare variants-desmoplastic, amelanotic, and polypoid malignant melanomas-are associated with local recurrences and metastatic lesions. Early diagnosis is the key to proper treatment and improved survival rate for patients with these unusual variants of melanoma. Increased awareness of the wide variety of clinical features of melanoma should lead to earlier diagnosis.

Amelanotic melanoma: cases studied by Fontana stain, S-100 immunostain, and ultrastructural examination.

We studied 15 cases of amelanotic melanoma by using light microscopy (in conjunction with Fontana staining and S-100 immunostaining) and electron microscopy. In 14 of the 15 cases, metastatic melanomas were present; 11 were associated with a history of pigmented primary melanoma. The Fontana stain was positive in 4 cases and negative in 11. The S-100 stain was positive in 13 cases and negative in 2. Of the 11 cases with negative Fontana stains, 9 were positive with the S-100 immunostain and 2 were negative. Electron microscopy showed melanosomes in 13 cases. Melanosomes were seen in the two cases with negative Fontana and S-100 staining. Although all stages of melanosomes were identified, generally the majority were immature melanosomes. This study demonstrates the difficulties associated with the histologic diagnosis of amelanotic melanoma. The Fontana stain may be helpful, and the S-100 stain is generally positive. Electron microscopy provided the only evidence for melanoma in two cases and is considered the most definitive method of diagnosis of amelanotic melanomas. These tumors generally produce some pigment and thus are called amelanotic by convention, not because pigmentation is totally absent.

Follicular mucinosis: histopathologic review of 33 cases.

Among 33 patients with the histologic diagnosis of follicular mucinosis (alopecia mucinosa) made at our institution between 1982 and 1989, 9 had mycosis fungoides diagnosed concomitantly. Three other patients had lymphoproliferative disorders, and two had Kaposi's sarcoma. Analysis of biopsy features such as epidermal lymphocytic exocytosis, periappendageal infiltrate, and deposition of mucin revealed no predominant finding that distinguished a benign course from mycosis fungoides. A predominance of eosinophils in the infiltrate was suggestive of benign follicular mucinosis rather than mycosis fungoides. Gene rearrangement studies detected three clones in three patients with follicular mucinosis; two were in patients with mycosis fungoides, and one was in a patient with dermatitis. The outcome of these three patients is pending further follow-up. No histopathologic or clinical features distinguished these patients from the others.

Neutrophilic dermatoses and myeloproliferative disease: report of two cases.

The term "neutrophilic dermatosis" has been suggested for a spectrum of skin lesions that have been noted in some patients with myeloproliferative diseases. These cutaneous conditions vary from plaques typical of Sweet's syndrome to bullous and pyodermatous lesions. We describe two patients with neutrophilic dermatoses and myeloproliferative disorders. Distinctive features included concurrent bullous pyodermatous lesions and characteristic lesions of Sweet's syndrome in one patient and overwhelming sterile pulmonary infiltration in the other patient. These disorders may be difficult to distinguish from acute infectious processes, and they may have systemic components, including pneumonitis. Possible therapeutic alternatives to systemic corticosteroid therapy are suggested.

Sweet's syndrome: systemic signs and symptoms and associated disorders.

OBJECTIVE: To characterize the findings associated with acute febrile neutrophilic dermatosis (Sweet's syndrome [SS]) and the response of SS to treatment. DESIGN: We retrospectively reviewed 48 cases of SS encountered at the Mayo Clinic between 1980 and 1992. MATERIAL AND METHODS: Histopathologic specimens and medical records were studied to determine initial manifestations, patterns of involvement, systemic signs and symptoms (including mucosal, musculoskeletal, hematologic, pulmonary, hepatic, and renal findings), and conditions associated with SS. RESULTS: In patients with SS, the typical manifestations are the acute onset of tender, erythematous or violaceous nodules or plaques in association with fever, leukocytosis, and dermal neutrophilia. In our study group, the cutaneous lesions most frequently involved the arms and legs. Of our 48 patients, 26 (54%) had a hematopoietic, plasma cell, or malignant disorder, and many of these patients had associated anemia, especially the male patients. No single laboratory finding specifically indicated an association with serious systemic disease. Most patients were treated with a tapering dose of prednisone, which yielded a good response. CONCLUSION: Clinical acumen and appropriate laboratory tests are the main requirements for detection of hematologic disorders, internal malignant diseases, or other systemic conditions associated with SS.

Aleukemic monocytic leukemia cutis.

Aleukemic leukemia cutis is a rare condition in which leukemic cells invade the skin before they appear in peripheral blood or bone marrow specimens. Herein we describe a 67-year-old man who underwent assessment because of papules and nodules on his back and lower extremities. A biopsy of these lesions confirmed a dense, predominantly monocytic infiltrate of the dermis and subcutaneous tissue. Immunohistochemical stains were positive for CD43 (Leu-22) as well as monocytic markers. Bone marrow and peripheral blood examinations failed to reveal leukemia. Treatment was based on the results of the skin biopsy, and the patient is doing well 1 year after therapy.

Cytosine arabinoside-induced vasculitis.

Dermatologic side effects of cytosine arabinoside (ara-C) are rare and most commonly occur after high-dose (more than 100 to 200 mg/m2 per day) therapy has been administered for several days. Although vascular reactions after combination chemotherapeutic regimens with ara-C have been anecdotally described, they have not been previously reported after single-agent chemotherapy with ara-C. Herein we describe two patients with acute nonlymphoblastic leukemia in whom cutaneous small vessel necrotizing vasculitis developed after high-dose single-agent chemotherapy with ara-C. Cutaneous lesions developed 3 to 5 days after initiation of therapy and resolved spontaneously within a week after the chemotherapeutic regimen was completed. No evidence of systemic vasculitis was present in either patient. Prior experimental data have demonstrated a direct toxic effect of ara-C on endothelial cells, and this outcome may represent the underlying mechanism of vascular injury.

Superficial granulomatous pyoderma: clinicopathologic spectrum.

Superficial granulomatous pyoderma is a form of pyoderma gangrenosum characterized by superficial ulceration and a chronic course. Histopathologic examination shows a granulomatous response. We report two new cases of superficial granulomatous pyoderma in detail and briefly review the clinical data of five previous cases included in a recent series. These lesions typically begin as single furunculoid papules that most commonly occur on the trunk and that may arise at sites of surgical treatment or other pathergic stimuli. The lesions progress to superficial ulcers with a relatively clean base and vegetative borders. Tetracycline, minocycline, sulfapyridine, dapsone, and intralesionally administered corticosteroids have been effective anti-inflammatory agents, producing healing and allowing avoidance of the use of systemic corticosteroids in the management of most patients with superficial granulomatous pyoderma.

Grover's disease: clinicopathologic review of 72 cases.

OBJECTIVE: To report the clinicopathologic findings in patients with Grover's disease. MATERIAL AND METHODS: We reviewed the medical records and biopsy specimens from 72 patients with transient acantholytic dermatosis (Grover's disease) examined at Mayo Clinic Rochester. Hematoxylin-eosin-stained biopsy specimens (from all patients) were assessed. Immunohistochemistry stains BRST-2, CAM 5.2, and CD44 were used to stain eight specimens. Direct immunofluorescence reports were reviewed. Selected specimens were stained by indirect immunofluorescence to detect major basic protein. RESULTS: Of the 72 patients, 63 (88%) were men, and the mean age was 48 years (range, 31 to 85). Lesions were distributed mainly on the trunk (in 71 patients) and proximal extremities (in 25). Heat and sweating frequently were exacerbating factors. Fifteen patients (21%) were bedbound. Concurrent nondermatologic malignant disease was present in 18 patients (25%). Two patients (3%) had acquired immunodeficiency syndrome. Follow-up in 28 patients (mean, 38 months; range, 3 months to 7 years) revealed that the disease had recurred in 13, persisted in 3, and resolved in 12. Review of the biopsy specimens showed that acantholysis was pemphigus vulgaris-like in 40 patients (56%), Darier's disease-like in 16 (22%), spongiotic in 12 (17%), pemphigus foliaceus-like in 2 (3%), and Hailey-Hailey disease-like in 2 (3%). A perivascular lymphocytic infiltrate of varied intensity in 64 specimens (89%) was associated with eosinophils in 16 (22%). In nine biopsy specimens with dermal eosinophilia stained for major basic protein, varied dermal cellular and extracellular deposition of major basic protein was present. Results of direct immunofluorescence studies, performed in 17 cases, were negative or nonspecific. CD44 stained acantholytic areas in addition to sweat glands in two of eight specimens (25%). CONCLUSION: Further studies of the pathogenesis of Grover's disease are needed. The predisposing conditions, site of involvement, and relapsing nature of this disorder may implicate acrosyringeal dysfunction as the cause.

Malignant pyodermas revisited.

The concept of malignant pyoderma (MP) has created controversy since its origin. The distinction of this disease from pyoderma gangrenosum was based on clinical criteria and response to treatment. Herein we discuss our current ideas on this entity and its possible relationship to Wegener's granulomatosis (WG). Follow-up data from the three original cases of MP are reported, as well as additional clinical and laboratory data from cases subsequently thought to represent MP. Many of these cases have similar clinical features such as facial and periauricular ulceration and occasionally signs or symptoms of WG, including positive titers of antineutrophil cytoplasmic antibodies (with a diffuse cytoplasmic staining pattern) (cANCA). MP represents a distinctive clinical disorder and may be a dermal manifestation of WG. Some cases of MP may represent pyoderma gangrenosum or other undefined systemic illnesses. Such cases of WG can be distinguished on the basis of clinical, histopathologic, and laboratory evidence including cANCA titers. MP should no longer be used as a final clinical diagnosis.

Chronic hepatitis C and skin diseases: a review.

OBJECTIVE: To emphasize the ongoing role of chronic hepatitis C virus (HCV) infection in the cause or exacerbation of severe dermatologic disorders. DESIGN: We present two case reports to outline the pertinent findings in hepatitis C-related cryoglobulinemia, leukocytoclastic vasculitis, and lichen planus and discuss the main disorders associated with chronic HCV infection. RESULTS: Chronic HCV infection has recently been recognized in association with various skin disorders. The most commonly reported association is the triad of leukocytoclastic vasculitis, cryoglobulinemia, and chronic HCV infection. Other cutaneous disorders associated with HCV infection include porphyria cutanea tarda, lichen planus, erythema nodosum, urticaria, erythema multiforme, and polyarteritis nodosa. CONCLUSION: Patients with onset or exacerbation of these disorders should undergo assessment for HCV infection.

Granulomatous vasculitis associated with herpes virus: a persistent, painful, postherpetic papular eruption.

Cutaneous granulomatous vasculitis manifesting as a postherpetic reaction pattern is uncommon hand has previously been reported as a delayed complication of varicella-zoster virus infection. We describe three patients who had persistent, painful, postherpetic papules in a zosteriform distribution that histologically demonstrated a small vessel granulomatous vasculitis. Herpes simplex virus DNA detected by the polymerase chain reaction technique was demonstrated in two cases.

Malignant blue nevus: a report of eight cases.

Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.