[Scurvy and acquired ichthyosis associated to Whipple's disease]. / Escorbuto e ictiosis adquirida asociadas a enfermedad de Whipple.

The skin manifestations, except for hyperpigmentation, are uncommon in Whipple's disease (WD). We present the case of a 48-year-old male with chronic diarrhea and long course general syndrome associated to neurological manifestations. Skin examination revealed lesions in the lower limbs and gums that were clinically consistent with scurvy and were confirmed by histological study and measurement of blood vitamin C levels. Furthermore, he had lesions that were clinically and histologically consistent with acquired ichthyosis. The digestive tract biopsy study showed non-necrotizing epithelioid granulomas without the presence of PAS positive macrophages. The patient was diagnosed of Whipple's disease through the identification of genomic fragments of Tropheryma Whippelii by PCR in duodenal samples. He was treated with antibiotics for two years with resolution of the cutaneous and digestive picture but with partial improvement of the neurological symptoms. In the literature reviewed, we did not find any case of acquired ichthyosis associated to WD and only one of scurvy secondary to this rare disease.

[Necrobiotic xanthogranuloma with scleroatrophic lichen associated with paraproteinemia]. / Xantogranuloma necrobiótico con paraproteinemia asociado a liquen escleroatrófico.

Necrobiotic xanthogranuloma (Xn) with paraproteinemia is a histiocytoxanthomatosis (non-X histiocytosis) that affects the dermis and subcutaneous tissue of the face and less frequently the trunk and limbs. We present the case of a 58-year-old woman with a previous background of IgG (lambda) paraproteinemia and multiple autoimmune diseases, that associate clinically and histologically typical lesions of Xn on face, neck and limbs and of lichen sclerosus et atrophius (LEA) on skin and mucosae. The treatments performed were ineffective, the Xn lesions followed a chronic and progressive course with increased number, size and ulceration of them. The paraproteinemia has remained stable since it was diagnosed eight years ago. We have not found the association of Xn with paraproteinemia and SAL described in the literature. We review the characteristics of this rare disease and its possible pathogenic mechanisms.

Escorbuto e ictiosis adquirida asociadas a enfermedad de Whipple / Scurvy and acquired ichthyosis associated to Whipple’s disease

Las manifestaciones cutáneas, a excepción de la hiperpigmentación, son poco frecuentes en la enfermedad de Whipple (EW). Presentamos el caso de un varón de 48 años de edad con diarrea crónica y síndrome general de larga evolución, asociado a manifestaciones neurológicas. En la exploración cutánea se observó en miembros inferiores y encías lesiones compatibles clínicamente con escorbuto, que se confirmó mediante estudio anatomopatológico y determinación de niveles de vitamina C en sangre. Así mismo, presentaba lesiones clínica e histológicamente compatibles con ictiosis adquirida. El estudio de la biopsia de aparato digestivo demostró granulomas epitelioides no necrotizantes sin la presencia de macrófagos PAS positivos. El paciente fue diagnosticado de enfermedad de Whipple mediante la determinación de fragmentos genómicos de Tropheryma Whippelii por reacción en cadena de la polimerasa (PCR) en muestras duodenales. Recibió tratamiento antibiótico durante dos años con resolución del cuadro cutáneo y digestivo, pero con mejoría parcial de la clínica neurológica. En la literatura revisada no hemos encontrado ningún caso de ictiosis adquirida asociada a EW, y sólo uno de escorbuto secundario a esta rara enfermedad

The skin manifestations, except for hyperpigmentation, are uncommon in Whipple's disease (WD). We present the case of a 48-year-old male with chronic diarrhea and long course general syndrome associated to neurological manifestations. Skin examination revealed lesions in the lower limbs and gums that were clinically consistent whit scurvy and were confirmed by histological study and measurement of blood vitamin C levels. Furthermore, he had lesions that were clinically and histologically consistent with acquired ichthyosis. The digestive tract biopsy study showed non-necrotizing epithelioid granulomas without the presence of PAS positive macrophages. The patient was diagnosed of Whipple's disease through the identification of genomic fragments of Tropheryma Whippelii by PCR in duodenal samples. He was treated with antibiotics for two years with resolution of the cutaneous and digestive picture but with partial improvement of the neurological symptoms. In the literature reviewed, we did not find any case of acquired ichthyosis associated to WD and only one of scurvy secondary to this rare disease

E-selectin polymorphism in erythema nodosum secondary to sarcoidosis.

OBJECTIVE: E-selectin is expressed on cytokine-stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. An A/C polymorphism at position +561 in the E-selectin gene, which yields an amino acid exchange from serine to arginine at position 128 in the epidermal growth factor-like domain, has been described. We have assessed whether this bi-allelic polymorphism may be implicated in the clinical expression of erythema nodosum (EN) secondary to sarcoidosis. METHODS: Thirty-one patients with biopsy-proven erythema nodosum (EN) associated with sarcoidosis, 68 patients with biopsy-proven EN related to other etiologies and 66 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for the A/C polymorphism gene by PCR-restriction fragment length polymorphism. RESULTS: A significantly reduced frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.019) and also compared to patients with EN unrelated to sarcoidosis (p = 0.028). This was also the case when the distribution of genotypes in patients with sarcoidosis was compared with that observed in patients with EN due to other etiologies (p = 0.028) and controls (p = 0.037). This was due to an absence in both C/A heterozygotes and C/C homozygotes in patients with EN secondary to sarcoidosis. CONCLUSIONS: The present study constitutes the first attempt to assess the influence of E-selectin polymorphism at position +561 in the development of sarcoidosis. The C allele at the +561 position of the E-selectin gene is associated with significantly reduced risk of developing sarcoidosis in patients with EN.

HLA-DRB1 associations in biopsy proven erythema nodosum.

OBJECTIVE: To examine the HLA-DRB1 associations of patients with erythema nodosum (EN), establish HLA-DRB1 differences among patients with idiopathic and secondary EN, and identify the HLA-DRB1 associations with specific conditions presenting with EN. METHODS: We conducted a retrospective study of 100 patients (83 women) with biopsy proven EN diagnosed for a defined population in Northwest Spain. Patients were classified into idiopathic or secondary if skin nodules occurred in the context of a well defined disease, or there was a precipitating event in close temporal relationship with the onset of EN. Patients and controls were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: At the time of diagnosis no precipitating events or underlying diseases were identified in 35 cases and, due to this, they were considered to be idiopathic. Although strong associations do not appear to exist between HLA-DRB1 and unstratified EN, the idiopathic group showed a significantly lower frequency of HLA-DRB1*04 phenotype compared with controls. Among the patients with secondary EN, the patient subgroup with sarcoidosis exhibited a significantly increased frequency of HLA-DRB1* 13 compared with healthy controls. CONCLUSION: Idiopathic and some groups of secondary EN seem to have different HLA-DRB1 associations. These differences may have prognostic value in identifying patients with specific conditions associated with this syndrome.

Erythema nodosum: etiologic and predictive factors in a defined population.

OBJECTIVE: To examine the frequency and features of erythema nodosum (EN), establish disease associations, and identify the optimal set of predictors for the occurrence of secondary EN. METHODS: We performed a retrospective study of an unselected population of patients 14 years and older with biopsy-proven EN diagnosed at a referral hospital between 1988 and 1997. Patients were classified as having either idiopathic EN or EN secondary to other diseases if the skin nodules occurred in the context of a well-defined disease, or if there was a precipitating event in close temporal proximity to the onset of EN. RESULTS: One hundred six patients (82 women) were diagnosed as having biopsy-proven EN. At the time of diagnosis, no precipitating events or underlying diseases were identified in 36.8% of patients. Sarcoidosis and nonstreptococcal upper respiratory tract infections (URI) were the most common conditions associated with secondary EN. Only 1 of 35 patients with an initial diagnosis of idiopathic EN and a followup of at least 1 year was finally diagnosed as having secondary EN. The best predictive model of secondary EN included an abnormal results on a chest radiograph, a previous history of nonstreptococcal URI, and a significant change in antistreptolysin O (ASO) titer in 2 consecutive determinations performed in a 2-4-week interval. Also, the presence of peripheral synovitis, a positive tuberculin skin test, and a history of diarrhea suggested the presence of secondary EN. This model showed high sensitivity and specificity. CONCLUSION: Idiopathic EN is common. A basic procedure including careful medical history-taking, a physical examination for peripheral synovitis, 2 consecutive ASO determinations, a tuberculin skin test, and chest radiography may be sufficient to diagnose EN.

[Ehlers-Danlos's syndrome type II. A family study]. / Síndrome de Ehlers-Danlos tipo II. Estudio familiar.

We describe the presence of EDS type II in a family whose diagnosis was lately established by medical consultation of one of its members suffering from hyperuricemia and gout. We stress the relevance of an early diagnosis of this syndrome as a means to prevent and reduce as much as possible cardiovascular, hemorrhagic and surgical systemic complications associated to this disease.