M. Megahed

Schönlein-Henoch purpura associated with gastric Helicobacter pylori infection

Schönlein-Henoch purpura is characterized by palpable purpura, colicky abdominal pain, gastrointestinal hemorrhage, arthralgias, and renal involvement. Bacterial and viral infections, as well as drugs and diseases associated with immune complexes, are thought to be responsible. We describe the case of a 21-year-old woman with Schönlein-Henoch purpura and chronic active gastritis with erosions. Helicobacter pylori was found in gastric mucosa using the newly introduced, nontoxic, noninvasive 13C-urea breath test; infection was confirmed by gastric mucosal biopsy. After eradication of H. pylori with omeprazole and amoxicillin, the skin changes, gastric complaints, and proteinuria disappeared. Ten months later, Schönlein-Henoch purpura recurred. H. pylori was again detected. After therapy, H. pylori was eradicated and the clinical manifestations faded. To our knowledge, H. pylori has not previously been described as a cause of Schönlein-Henoch purpura.

Phototesting in lupus erythematosus tumidus--review of 60 patients.

Photosensitivity is an important characteristic feature of several forms of lupus erythematosus (LE), and induction of skin lesions by UV‐A and UV‐B irradiation has been proved to be an optimal model for evaluating light sensitivity in patients with this disease. Because lupus erythematosus tumidus (LET) has rarely been documented in the literature and is often difficult to differentiate from other photodermatoses such as polymorphous light eruption, we performed photoprovocation tests in 60 patients with LET according to a standardized protocol. Areas of uninvolved skin on the upper back were irradiated with single doses of UV‐A (100 J/cm2) and/or UV‐B (1.5 minimal erythema dose) daily for three consecutive days. Interestingly, patients with LET are more photosensitive than those with subacute cutaneous lupus erythematosus, and in our study experimental phototesting revealed characteristic skin lesions in 43 patients (72%). Because of the latency period in developing positive phototest reactions, it might be difficult for these patients to link sun exposure with their skin lesions. Furthermore, our data revealed a positive correlation of antinuclear antibodies and positive provocative phototest reactions in these patients as seen for other forms of LE. In conclusion, the high incidence of positive phototest reactions in correlation with the clinical findings, history of photosensitivity and antinuclear antibodies enable the classification of LET as the most photosensitive type of LE.

Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas

Abstract Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.

Reliability of diagnosis of melanoma in situ.

Early and correct diagnosis of malignant melanoma is of utmost importance to ensure adequate treatment and the best outcome. Prompted by the death of a patient with an apparent metastasising melanoma in situ, we reassessed 104 people with this malignant disorder, whose diagnosis had been histopathologically verified. We did immunohistochemical analysis of cells with the melanocytic marker melan-A/MART-1, and results of this analysis showed that 30 (29%) of 104 patients had invasive melanomas. One patient died of distant metastases, and the tumour recurred in another. Our finding could be relevant for diagnosis and treatment of melanoma in situ.

Epidermolysis bullosa acquisita — successful treatment with colchicine

The treatment of epidermolysis bullosa acquisita (EBA) is difficult and often disappointing. We report on the successful treatment of two EBA patients with colchicine. The drug was administered orally at an initial dose of 2 mg/day. After 2 weeks of therapy a dramatic improvement was observed. Most of the cutaneous and buccal mucosal lesions had healed and both of the patients were able to go about their normal daily activities. In the first patient the disease was refractory to dapsone alone or combined with steroids. In the second patient no other treatment was tried. After 6 months a maintenance dose of 1 mg/day colchicine was given. The disease had remained stable in both patients at the time of writing for more than 8 months. No side effects were observed. We suggest that colchicine may be a helpful and safe drug for patients with EBA.

CHILD syndrome in a boy

CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) occurs, as a rule, exclusively in girls because the underlying X-linked gene exerts a lethal effect on male embryos. In this report the characteristic manifestations of CHILD syndrome are described in a 2-year-old boy with a normal chromosome constitution 46,XY. This exceptional case is best explained by the assumption of an early somatic mutation and thus compatible with the concept of X-linked dominant male-lethal inheritance of this trait.

Palisaded encapsulated neuroma (solitary circumscribed neuroma). A clinicopathologic and immunohistochemical study

Although palisaded encapsulated neuroma was first described over 20 years ago, it has received little attention. We present the clinical, histopathologic, and immunohistochemical features of 10 cases of this entity. The cases were studied by routine light-microscopic examination and immunohistochemistry using the avidin-biotinperoxidase technique. Clinical information and follow-up data were obtained from the hospital records. The lesions were solitary, asymptomatic, skin-colored papules that were located on the faces of patients who ranged in aged from 37 to 66 years (average, 52 years). The female to male ratio was 1:1. None of the patients had von Recklinghausens disease, and none of the lesions recurred after excision. Histopathologically, the tumors were well circumscribed and situated predominantly in the dermis. They were encapsulated and composed of spindle cells arranged in interlacing fascicles. The tumor cells were positive for S-100 protein. The capsule was composed of flattened, elongated cells that showed positivity for epithelial membrane antigen (EMA).

Coadministration of the new macrolide immunosuppressant RAD and mycophenolate mofetil in experimental corneal transplantation

Introduction. The effect of RAD, a new macrolide immunosuppressant, was examined as mono- and combination therapy with mycophenolate mofetil (MMF) in prevention of acute allograft rejection in murine corneal transplantation. Methods. Both drugs were administered orally for 18 days beginning at the day of transplantation. The inbred strains Fisher and Lewis were used as donors and recipients, respectively. Five groups were involved: syngeneic control, allogeneic control, 2.5 mg/kg RAD, 40 mg/kg MMF, and double drug therapy with 1.5 mg/kg RAD and 20 mg/kg MMF. Results. The median transplant survival time in the allogeneic combination was 12 (±0.3) days. Monotherapy with 2.5 mg/kg RAD and 40 mg/kg MMF led to a statistically significant prolongation of transplant survival to 25.5 (±12.5, P =0,0001) days and 19.5 (±13.9, P =0.0053) days, respectively. Combination therapy was superior to both monotherapies (100±15.8 days, P =0.03). There was a significant reduction in the number of CD4+, CD8+, as well as CD45RA+ cells in the RAD- and double drug-treated animals when compared with the allogeneic control. This significant reduction in graft-infiltrating lymphocytes has not been found in the MMF monotherapy. Conclusions. The unique finding of this first study on the combination of RAD and MMF in murine corneal transplantation is that double drug therapy produces a highly synergistic effect in prevention of acute allograft rejection without a higher incidence of complications related to drug toxicity or overimmunosuppression.

Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus

Abstract. Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.

Synergism of RAD and cyclosporin A in prevention of acute rat corneal allograft rejection

Purpose. The novel immunosuppressant RAD, 40-0-(2-hydroxyethyl)-rapamycin, has synergistic effects with cyclosporin A. The aim of this study was to evaluate the combined effect of RAD and cyclosporin A in the prevention of acute allograft rejection after murine corneal transplantation. Methods. Fisher donor corneas were implanted into Lewis recipients. Postoperative evaluation included slit-lamp biomicroscopy and immunohistology. Treatment groups were comprised of rats treated orally with RAD 2.5 mg/kg/day, cyclosporin A 10 mg/kg/day, RAD 1.5 mg/kg/day plus cyclosporin A 5 mg/kg/day. Results. Therapy with RAD 2.5 mg/kg and cyclosporin A 10 mg/kg led to a statistically significant and comparable prolongation of transplant survival. However, combination therapy was significantly superior. There was a significant reduction in the number of infiltrating cells in the animals treated with RAD and cyclosporin A. Conclusions. This is the first study on the efficacy of a double drug regimen with RAD and cyclosporin A for the control of acute corneal allograft rejection. Combination therapy resulted in superior graft survival.