Successful multimodality treatment of recalcitrant necrobiotic xanthogranuloma using electron beam radiation and intravenous immunoglobulin.

Necrobiotic xanthogranuloma (NXG) is a rare dermatosis with a poorly understood pathophysiology. Studies comparing treatments for such lesions are limited. We present the case of a patient with a 30-year history of NXG refractory to several individual therapeutic interventions [excision, intravenous immunoglobulin (IVIg), systemic chemotherapies and immunosuppressants, cryotherapy and laser therapy], who ultimately responded to a combination of treatment with electron beam radiation therapy (EBRT) in conjunction with IVIg. This combined treatment resulted in flattening of the NXG lesions and a reduction of symptomatic pruritus within the treatment zone. EBRT may represent a potent treatment for NXG, and formal trials evaluating its effectiveness may yield insights into the management of NXG.

Neoplasias sólidas de células redondas en edad pediátrica: correlación entre diagnóstico morfológico e inmunohistoquímica / Solid neoplasm of circle celis in the pediatric age: correlation between morphological and immunohistochemistry diagnóstic

Precisar la importancia de realizar el estudio de inmunohistoquímica y su correlación con el diagnóstico anatomopatológico de rutina para el diagnóstico de los tumores sólidos malignos de células redondas en pacientes pediátricos. Se realizó un estudio transversal, descriptivo, retrospectivo no experimental. Se estudiaron 147 pacientes con diagnóstico de neoplasia de células redondas, de los cuales 96 cumplieron con criterios de inclusión. La mayor frecuencia de casos la obtuvo el linfoma No Hodgkin (20,8%), seguido del linfoma de Hodgkin (15,6%) y tumor de Wilms (17,7%). El grupo etario mayormente afectado fue el escolar (37,5%). El género predominante fue el masculino (60,4%). Las manifestaciones clínicas más frecuentes fueron masa palpable (76,04%), fiebre(44,79%), anemia (41,67%), dolor (41,30%) y pérdida de peso (33,33%). Se evidenció la mayor correlación diagnóstica en el tumor de Wilms (100%), seguido del linfoma No Hodgkin (80%) y el linfoma de Hodgkin (75%); la menor correlación la presentaron el sarcoma de Ewingy el neuroblastoma (41,7%, ambos). La correlación total resultó “considerable” según la fuerza de concordancia del coeficiente de Kappa (k: 0,601. P=0,000). Se requiere la integración del examen histopatológico de rutina como método diagnóstico de pesquisa y del estudio de inmunohistoquímica como método auxiliar diagnóstico, para determinar la histogénesis de las neoplasias, descartar diagnósticos diferenciales, realizar un diseño terapéutico apropiado y precisar el pronóstico.

To precise the state and the importance o fthe study of immunohistochemistry and its correlation with the routine pathological diagnosis to use in diagnosis of malignant solid tumors of round cells in pediatric patients. We was performed a transversal, descriptive and retrospective non-experimental study. We studied 147 patients diagnosed with round cell tumor, 96 of them weremet in inclusion criteria. The highest frequency of the cases was Non-Hodgkin lymphoma (20.8%), followed by the Hodgkin lymphoma (15.6%) and the Wilms tumor(17.7%). The age group most affected was the school(37.5%). The male gender was the predominant (60.4%).The most frequent clinical manifestations were a palpablemass (76.04%), the fever (44.79%), the anemia (41.67%),the pain (41.30%) and the weight loss (33.33%). Evidencedthe highest correlation in the diagnosis of Wilms tumor(100%), followed by Non-Hodgkin lymphoma (80%) and Hodgkin lymphoma (75%); showed the lowest correlation between the Ewing sarcoma and neuroblastoma (41.7%, both). The total correlation is “considerable” accordingto strength of agreement the Kappa coefficient (k: 0.601.P=0.000). It requires the integration of routine histopathological examination as diagnostic method of research and study of immunohistochemistry as an auxiliary diagnostic method to determine the histogenesis of neoplasm and exclude the differential diagnoses, make anappropriate therapeutic design and the determine prognosis of this group of patients.

Increased vascular endothelial growth factor mRNA expression in the heart of streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate vascular endothelial growth factor (VEGF), fms-like tyrosine kinase 1 (flt-1), and fetal liver kinase (flk-1) expression in the heart of experimental diabetic rats. Ten young adult male Wistar rats (5 streptozotocin [STZ]-induced diabetic rats, without insulin treatment, and 5 controls) were studied. Ninety days after the induction of diabetes, semiquantitative reverse transcription (RT)-polymerase chain reaction (PCR) coamplification of VEGF/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcription was performed. RT-PCR was also performed for VEGF receptors flk-1 and flt-1. VEGF mRNA expression, at 234 bp, was detectable in the heart of the rats and was significantly higher in those with diabetes. Densitometric analysis of PCR products showed that VEGF mRNA levels were meanly 4.8-fold higher in STZ-induced diabetic rats than controls (VEGF/GAPDH densitometric ratio, 3.46 +/- 0.20 v 0.74 +/- 0.10, P <.001). No significant difference was found in flt-1 and flk-1 amplification products between STZ-induced diabetic rats and controls (flt-1/GAPDH densitometric ratio, 0.58 +/- 0.01 v 0.64 +/- 0.05, P>.1; flk-1/GAPDH densitometric ratio, 0.66 +/- 0.10 v 0.7 +/- 0.06, P >.2). The increase in VEGF mRNA expression observed in this experimental diabetic model is in contrast with the typical impairment in collateral vessels of diabetic hearts. This apparent discrepancy might be explained by a resistance of cardiac tissue to VEGF. The lack of mRNA flt-1 and flk-1 overexpression in diabetic hearts could be one of the mechanisms for this resistance.

Update on leprosy in immigrants in the United States: status in the year 2000.

The World Health Organization established a goal in 1991 of "elimination of leprosy as a public health problem by the year 2000." Although prevalence rates of leprosy have decreased in many geographic areas, it is clear that in some countries where leprosy is endemic, such as Brazil and India, this goal will not be reached. Leprosy is rare in the United States, but 85% of detected cases are in immigrants in whom the disease may mimic many common dermatologic and neurological entities, leading to delay of diagnosis. The statuses of polymerase chain reaction analysis, serological testing, and vaccines are reviewed. Effective multidrug therapy and prevention of permanent damage to nerves by early recognition and treatment will help prevent residual disabilities. This update reviews what is known about the pathophysiology and treatment of leprosy. Increased awareness will lead to earlier recognition, diagnosis, and treatment.

[Learning plans: experience with an innovative approach to nursing education]. / I piani di apprendimento: l'esperienza di un approccio innovativo nella formazione infermieristica.

According to the literature, self-learning plans represent an helpful and very flexible method in order to individualize the nursing students' learning activities, to develop the students' autonomy and responsibility together with the skills required for continuing nursing education. The educational experience of the implementation of the self learning plans in the practical training of the nursing students of the Pediatric Nursing School of Trieste, during 1996-97, is described. The 9 third year students produced 27 learning plans. According to the mentors and the students, the overall experience had a positive impact. The presentation and evaluation of the learning plans spurred the students' initiative, the adoption of innovative learning and research strategies and allowed to replace the traditional classroom teaching lectures. The main problems related to the implementation of this method lay in the increase of mentors' workload and in the difficulties in matching the high flexibility of the method with the inflexibility and constraints of both the organization and teaching programs and paces.

Side effects of alpha-interferon therapy and impact on health-related quality of life in children with chronic viral hepatitis.

BACKGROUND: Interferon (IFN) is standard therapy for chronic viral hepatitis in children. The aim of this study was to evaluate the side effects of alpha-interferon (IFN) in 94 consecutive children (58 males; age range, 3 to 14 years) affected by chronic viral hepatitis treated with different schedules ranging from 3 to 10 MU and from 3 to 12 months, and the impact of this therapy on health-related quality of life. METHODS: Side effects were evaluated with clinical and laboratory examinations and were recorded on a diary card. The health-related quality of life was evaluated with a modified version of the Sickness Impact Profile. RESULTS: All patients experienced at least one adverse reaction to IFN treatment; 80% had more than five side effects. There were no life-threatening reactions. Three children experienced severe reactions (febrile seizure, severe hypertransaminasemia and relapsing episodes of epistaxis, respectively) that required permanent IFN withdrawal. Another child had a febrile seizure requiring temporary IFN withdrawal. In seven children the neutrophil count fell below 1000/mm3 and promptly increased when IFN was temporarily discontinued. The remaining children had mild or moderate clinical and/or laboratory adverse reactions. Age, sex, viral etiology of chronic hepatitis and response to therapy were not significantly associated with the appearance of side effects. The pre-IFN health-related quality of life was good in all children; it deteriorated significantly during IFN therapy and returned to basal standards within 3 months after IFN withdrawal. No patient required suspension of IFN therapy because of worsening of health-related quality of life. CONCLUSION: Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.

Clofazimine: a review of its medical uses and mechanisms of action.

Clofazimine has been in clinical use for almost 40 years, but little is known of its mechanism of action. The primary indication for clofazimine is multibacillary leprosy, but it is useful in several infectious and noninfectious diseases, such as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus erythematosus. Postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2. Clinical experience, possible mechanisms of action, and side effects of clofazimine are summarized.

Dermatomyositis update.

Dermatomyositis (DM) is an idiopathic, inflammatory myopathy characterized by dermatologic changes, myopathy, some typical serologic findings, and frequent extramuscular involvement. Both children and adults may be affected, with certain features distinct to children. Dermatologic changes may occur without myositis in patients with amyopathic DM. DM has been reported to occur in patients undergoing treatment with certain therapeutic agents or with concomitant infections. DM may be associated with malignant disease in older patients. Newer serologic tests may identify subsets with different clinical patterns and prognoses. Magnetic resonance imaging is increasingly used to identify muscle involvement and to select sites for biopsies. Newer studies provide improving guidance for therapies in steroid nonresponders.

Vascular skin ulcers of limbs.

On clinical grounds, ulcers of the leg of vascular origin can fairly easily be separated into venous and arterial origins; 85% of ulcers of the leg are caused by venous insufficiency. The ulcers occur mainly around the medial malleolus, are covered by moist granulation tissue, and are surrounded by varying degrees of stasis dermatitis and brown hemosiderin pigmentation. The limb is usually edematous and improves with elevation. In contrast, arterial ulcers of the leg develop more distally on the toes or feet, severe pain is a prominent feature, and the dry crusted ulcers usually lack granulation tissue. Elevation of the leg aggravated the pain of ischemic ulcers, whereas dependency of the limb provides some relief. Both types of ulcers heal faster with occlusive dressings that furnish a moist wound environment. Patients with ulcers caused by venous insufficiency can have coexisting peripheral atherosclerosis. Compression elastic stockings used for venous insufficiency should not be so tight that they induce necrosis of the skin in patients with occult arterial disease.

Mononuclear phagocytic and dendritic cell systems.

This review presents a classification scheme for disorders of the mononuclear phagocyte and dendritic cell systems. Previous classifications, based primarily on cytomorphology, are now obsolete. Electron microscopy, enzyme histochemistry, and, especially, immunocytochemistry have revealed the histiocyte identified by hematoxylin-and-eosin staining to be not one but several cell types. Currently, two broad groups of histiocytic cells are recognized, the monocyte-macrophage group and the dendritic cells. Dendritic cells are further subclassified as Langerhans cells, indeterminate cells, interdigitating cells, and dermal dendrocytes. Many disorders of the skin and other organs are characterized by proliferation of "histiocytic"-appearing cells. Some of these diseases clearly behave in a malignant fashion, whereas others follow a benign or variable course. At present, the proliferating cell type has been identified in only a few of these disorders by ultramicroscopy and cytochemical and immunocytochemical methods. Nevertheless, the pieces of the puzzle are beginning to fall into place. In general, those disorders that typically behave in a malignant fashion have been more extensively studied. The benign histiocytic disorders of children and adults are a heterogeneous group of diseases. Currently, some of these disorders are unclassified or classified with uncertainty. For example, how should severe histiocytosis with massive lymphadenopathy be classified? There is a proliferation of nonlymphoid mononuclear cells that are positive for S-100 protein and negative for CD1 and that exhibit lymphophagocytosis. Is this then a mononuclear phagocytic or dendritic cell disorder? Juvenile xanthogranuloma is a disorder of macrophages. Self-healing reticulohistiocytosis and solitary Langerhans cell histiocytoma are benign proliferative disorders of Langerhans cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary histiocytic dermatoses.

The physiology of the histiocyte (macrophage) in health and disease is reviewed briefly. An overview of the so-called primary malignant, pseudomalignant, and benign histiocytic disorders, excluding histiocytosis X, is presented. The malignant histiocytosis with erythrophagocytosis, the pseudomalignant histiocytic diseases (such as sinus histiocytosis with massive lymphadenopathy and regressing atypical histiocytosis), and the solitary lesions with histologic malignant and atypical storiform histiocytosis are described. Two groups of adult histiocytic diseases are reviewed; one is characterized by nonfamilial and familial histiocytic dermatoarthritis and the other by multiple widespread benign lesions, such as xanthoma disseminatum, generalized eruptive histiocytoma, nodular non-X histiocytosis, and various xanthomatous eruptions associated with paraproteinemia. Finally, multiple benign cutaneous histiocytic lesions of childhood, such as juvenile xanthogranuloma and congenital self-healing histiocytosis, are included.

Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia.

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

Sarcoidosis. An updated review.

Sarcoidosis, a multisystem disease of unknown cause characterized by the formation of noncaseating granulomas, may involve any organ of the body, but the commonest sites of predilection are the lungs, lymph nodes, skin, and eyes. Sarcoidosis can be associated with polyclonal hyperglobulinemia, hypercalcemia, hypercalciuria, circulating immune complexes, cutaneous anergy, and in vitro depressed cell-mediated immunity. Recent studies of the cellular composition and cellular interactions of sarcoid-involved tissue have resulted in some insight into the pathophysiology of the disease. In early stages the predominance of activated T-helper cells in affected sites may account for many of the immunologic aberrations. The production of macrophage chemotactic substances by these cells may be the initial stimulus for the formation of the granuloma. The natural history of the disease is highly variable; the acute forms tend to resolve spontaneously, whereas the chronic forms rarely involute. Although multiple therapeutic modalities have been used and some have reportedly been effective, systemic corticosteroids remain the most effective available therapeutic agents.