Interferon and low doses of methotrexate versus interferon and retinoids in the treatment of refractory/relapsed cutaneous T-cell lymphoma.

OBJECTIVES: Treatment of refractory/relapsed cutaneous T-cell lymphoma (CTCL) remains controversial, most studies included a few patients with a short follow-up. Previously, we performed two small studies employing interferon alpha 2b (IFN) combined with low doses of methotrexate (MTX) or retinoids. Thus, we conducted an open-label clinical trial to assess the benefit and toxicity of the two mentioned regimens in a large number of patients with a longer follow-up of the treatment of refractory/relapsed CTCL. PATIENTS AND METHODS: Three-hundred and seventy-seven patients with refractory/relapsed, pathologically confirmed, CTCL, with advanced stages and at least treated with two previous effective regimens in CTCL, were randomized to receive IFN and low doses of MTX compared with IFN and all trans-retinoid acid during 6 months; if a complete response (CR) was not achieved, treatment was continued until 12 months in both arms. At this time, if patient achieves CR, MTX or retinoid was stopped, and the patient continues to receive IFN until progression disease or toxicity. One-hundred and eight patients received IFN for more than 5 years. RESULTS: Toxicity was minimal and well tolerated, no patients needed to modify the administration of IFN secondary to toxicity. The overall complete response was achieved 80% in both arms. Actuarial curves at 5 years showed that progression-free survival was 60% in the IFN/MTX group and 62% in the IFN/retinoids group (P = 0.8) that were not statistically different and overall survival (OS) rates were 70 and 67%, respectively (P = 0.03). DISCUSSION: Both present schedules showed good tolerance and an excellent OS at 5 years, which is better than the other, more expensive and toxic, regimens. Considering the indolent course of CTCL, we suggested that those regimens, mentioned in this paper, will be regarded as the standard therapy, for patients of this setting. CONCLUSION: The use of IFN and retinoids or low dose of cytotoxic drugs will be preferred in patients with refractory/relapse CTCL, because OS is good and toxicity is minimal.

Cutaneous amebiasis: 50 years of experience.

Although cutaneous amebiasis (CA) is a rare disease, it is a public health concern worldwide, particularly in developing nations. It gains importance because of its severe clinical course, which can be confused with other disorders. Therefore, knowledge of its clinical features, histopathology, and pathogenesis is essential. We present a retrospective analysis over 50 years of 26 patients with CA who were diagnosed and treated at 2 Mexican institutions. Our main focus was to draw clinical information to identify mechanisms by which amebae reach the skin, occurring in a relatively small percentage of infected individuals. The recorded data included age and sex of the patients, form of presentation, any associated illnesses and/or factors, and methods for diagnosis. Histologic slides were reviewed in all cases; cytologic preparations also were available for 6 cases. Most patients were male (overall male to female ratio, 1.9 to 1). The disease always presented as painful ulcers containing varying amounts of amebae microscopically; the amebae were fairly easy to identify with routine stains, particularly when examination of tissue or smears was prepared from the edges of the ulcer instead of the necrotic centers. Erythrophagocytosis by the trophozoites was found and represented an unequivocal sign of its pathogenicity. We review the 2 mechanisms by which the organisms reach the skin. Most cases resolve with the use of specific antiamebic drugs; however, if left untreated, progression is rapid and unrelenting, sometimes with massive destruction of skin and subcutaneous tissues. Therefore, CA is a particularly virulent form of amebiasis.

Lucio's phenomenon is a necrotizing panvasculitis: mostly a medium-sized granulomatous arteritis.

Lucio's phenomenon (LPh) is a vasculitis clinically described in 1852 and microscopically documented in 1948 in patients with diffuse lepromatous leprosy; however, at present, there is no a clear concept about the pathogenesis of the necrosis, or about the type, size, and site of the damaged vessel. The objective of this study was to elucidate the type, size, site, and form of vessel damage in LPh in a retrospective, clinical, and histopathological study. Clinical information was obtained from the charts and records and/or from the histopathology request. Slides stained with hematoxylin and eosin, Ziehl-Neelsen, and Fite-Faraco were retrieved from our files. Direct immunofluorescence had been performed in 6 cases. Twelve cases fulfilled clinical evidence to make unequivocal diagnosis of diffuse lepromatous leprosy with LPh. All of them had necrotic, irregular, purpuric, and/or ulcerative lesions, which under the microscope showed medium-sized arteries, with their walls involved by clusters of macrophages containing large amounts of bacilli, distortion of the structure of the vessel wall, narrowing, and obliteration of their lumen. Smaller vessels showed changes of the leukocytoclastic type. LPh is a distinctive type of granulomatous and necrotizing panvasculitis; the involved vessels are mostly medium-sized arteries, located deeply in the skin, at the base, and within the hypodermis, but any other vessel is likewise involved, their occlusion leads to ischemic necrosis of the whole skin, frequently with detachment of the epidermis. These changes explain clearly and logically the clinical features observed more than 150 years ago.

Cutaneous amebiasis in pediatrics.

BACKGROUND: Cutaneous amebiasis (CA), which is still a health problem in developing countries, is important to diagnose based on its clinical and histopathologic features. OBSERVATIONS: Retrospective medical record review of 26 patients with CA (22 adults and 4 children) treated from 1955 to 2005 was performed. In addition to the age and sex of the patients, the case presentation, associated illness or factors, and method of establishing the diagnosis, clinical pictures and microscopic slides were also analyzed. CONCLUSIONS: Cutaneous amebiasis always presents with painful ulcers. The ulcers are laden with amebae, which are relatively easy to see microscopically with routine stains. Erythrophagocytosis is an unequivocal sign of CA. Amebae reach the skin via 2 mechanisms: direct and indirect. Amebae are able to reach the skin if there is a laceration (port of entry) and if conditions in the patient are favorable. Amebae are able to destroy tissues by means of their physical activity, phagocytosis, enzymes, secretagogues, and other molecules.

Immunization with a tetramer derivative of an anti-inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver.

Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.

Enfermedad de Paget extramamaria y mamaria, anaplásica y acantolíca: presentación de 7 casos y revisión de la literatura / Paget disease, extrammamary and mammary, anaplastic, acantholytic: a report of 7 cases and review of the literature

La enfermedad de Paget extramamaria anaplásica y acantolítica (EPeMAA) y la enfermedad de paget mamaria anaplásica y acantolítica (EPMAA), son formas raras de la EP; no se sabe en el momento actual su frecuencia real. Se presentaron por arriba de la cuarta decada, en 4 mujeres y 3 hombres. Su evolución fué crónica, clínicamente fueron placas verrugosas, ulceradas, facilmente sangrantes, bien limitadas. Clínica e histológicamente se confundieron con enfermedad de Bowen y con el pénfigo vegetante. Microscópicamente se observó en todo el espesor de la epidermis células anaplásicas pequeñas, con núcleo ovoide, cromatina fina sin disqueratosis, escaso citoplasma; la acantólisis fué acentuada con formaciones vegetantes. Se observaron células clásicas de Peget en forma alterna; todos exhibieron ulceración y en la periferia la imagen típica de EP. En la base de la neoplásia hubo infiltrado linfocitario en banda "patrón liquenoide". En 4 de los casos se identificó neoplásia maligna sincrónica en la profundidad (1 caso Ca de conductos mamarios, 2 casos Ca de conductos de glándulas apócrina y 1 caso de Ca. de conductos de glándulas ecrina de tipo esclerosante) fueron positivos al antígeno carcinoembrionario (ACE) 5/5, al antígeno de membrana epitelial (AMA) 5/5, y a la citoqueratina de bajo peso molecular (Cqbpm) 5/5. Hay que hacer el diagnóstico diferencial con la enfermedad de Bowen (EB), melanoma de diseminación superficial (MMDS) y con el pénfigo vegete. No hay diferencias en pronóstico entre la EP mamaria y extramamaria clásica y la EPeMAA u EPMAA

Espondilitis anquilosante y síndrome de Sjögren

La presencia de Síndrome de Sjögren (SS) en pacientes con espondilitis anquilosante (EA) es practicamente desconocida. Se estudiaron 37 sujetos con diagnóstico definitivo de EA: 31 hombres y 6 mujeres con un promedio de edad de 38 años y una evolución de la EA de 13.8 ñ 8.6 años. A todos los pacientes se les interrogó sobre manifestaciones de xerostomía y xeroftalmía; se les realizó además revisión oftalmológica, prueba de Schirmer, sialografía bilateral y biopsia de glándula salivar menor. De los 37 pacientes, 15 (40.5 por ciento) no presentaron anormalidad alguna y 22 (59.4 por ciento) tuvieron manifestaciones sintomáticas u objetivas de SS. En once pacientes (29.7 por ciento) se obtuvo una valoración oftalmológica anormal; 9 (24.3 por ciento) presentaron alteración en la sialografía y en 15 de 37 biopsias de glándula salival menor (40.5 por ciento) se observaron alteraciones histológicas. Dos pacientes (5.4 por ciento) tuvieron diagnóstico definitivo de xerostomía y tres pacientes (8.1 por ciento) diagnóstico definitivo de SS. La ausencia de reportes de SS en pacientes con EA sugiere que esta asociación es poco frecuente; sin embargo, el porcentaje encontrado en los pacientes con EA es mayor al reportado en la población general sana y población senil sana