Calcinosis of the cutis and subcutis: an unusual nonimmunologic adverse reaction to subcutaneous injections of low-molecular-weight calcium-containing heparins.

BACKGROUND: Local side effects at the injection sites of low-molecular-weight heparins are rare and can be of immunologic or nonimmunologic origin. Calcinosis cutis is a rare disorder and occurs in various circumstances. In patients with chronic renal failure the risk of pathologic calcifications is raised due to elevated calcium-phosphorus products. OBJECTIVE: Five patients suffering from renal failure developed remarkable cutaneous and subcutaneous nodules or plaques following subcutaneous nadroparin-calcium injections. Our aim was to evaluate the morphology and precipitation factors of these calcifications and to discuss immunological and nonimmunological differential diagnoses. METHODS: Histological examination, spectroscopic analysis, ultrasonography, allergy testing and reexposition testing including non-calcium heparins were performed. RESULTS: Histology using the van Kossa staining technique revealed calcinosis of the dermis and subcutis. Ultrasonography showed focal subcutaneous calcifications. In all patients the calcium-phosphorus products were elevated. CONCLUSION: Clinicians should be aware that patients with renal failure and elevated calcium-phosphorus products may be at risk of developing calcinosis cutis at calcium-containing heparin injection sites. As a consequence, we propose the use of non-calcium heparins in these patients.

Increased expression of VEGF in glomeruloid reactive angioendotheliomatosis.

Reactive angioendotheliomatosis (RAE) is a very rare disorder characterized by marked proliferation of endothelial cells. It is often associated with infections, such as subacute bacterial endocarditis, but has also been described as an early sign of a developing hematological malignancy. We report the case of a 71-year-old Caucasian female who developed lupus-like RAE lesions. A thorough diagnostic workup and subsequent 3-year clinical follow-up revealed no sign of an underlying infectious or neoplastic disorder. Repetitive serum immunofixations were only once consistent with a monoclonal gammopathy of undetermined significance. In lesional skin, the pronounced bud-like endothelial cell formation was associated with an increased epidermal expression of vascular endothelial growth factor (VEGF), a potent angiogenic mediator. In accordance with the paracrine action of epidermally derived VEGF, vascular endothelial cells in lesional skin revealed increased expression of the VEGF receptor VEGFR-2 (KDR). This case suggests a possible role of epidermally derived VEGF in endothelial cell proliferation in RAE.

Long-term efficacy, curative potential, and prognostic factors of radiotherapy in primary cutaneous B-cell lymphoma.

PURPOSE: Primary cutaneous B-cell lymphomas (PCBCL) are rare and constitute approximately 5-10% of all cutaneous lymphomas. In the literature, conflicting data exist on the optimal treatment modality regarding the efficacy and the relapse rate after radiotherapy (RT) or polychemotherapy. To evaluate the efficacy of RT, patient data from two centers were analyzed and compared with recent reports in the literature. MATERIALS AND METHODS: Between April 1984 and June 2001, 35 patients with PCBCL, 17 men and 18 women ages 27-86 years, were treated with RT alone (29/35 patients) or postoperative RT (6/35 patients). According to the European Organization for Research and Treatment of Cancer classification for PCBCL, this study group included 21 patients (60%) with primary cutaneous follicle center-cell lymphoma, 7 (20%) with primary cutaneous immunocytoma, 4 (11%) with primary cutaneous large B-cell lymphoma (PCLBCL) of the leg, and 3 (9%) provisional types. RESULTS: A total of 34/35 patients achieved an initial complete response after RT. In one additional patient, RT was interrupted after 16 Gy because of fulminant pneumonia. A total of 11/35 (31%) patients developed cutaneous relapse after a median of 11 months. Three patients developed an in-field response and 8 patients an out-field relapse. After a median follow-up of 52 months, 27/35 patients are alive, whereas 8/35 patients died (three deaths resulting from PCBCL and five unrelated to PCBCL). The 5-year overall survival rate was 75% (95% CI: 55-95%). The 5-year relapse-free survival was 50% (95% CI: 32-68%). Univariate and multivariate analysis revealed disseminated primary lesions in at least two noncontiguous anatomic sites and the histologic subtype PCLBCL as unfavorable prognostic factors. CONCLUSIONS: RT of all visible skin lesions is an effective treatment for localized PCBCL. In patients with cutaneous relapses, RT is an effective treatment option as well.

Acral erythrodysesthesia syndrome caused by intravenous infusion of docetaxel in breast cancer.

Docetaxel-induced skin reactions include hypersensitivity, edema, skin toxicity with erythrodysesthesia syndrome, infusion site reactions, alopecia, nail onycholysis, nail pigmentation, photosensitivity, scleroderma, and others, for example, stomatitis and paresthesias. However, of all reported effects, the acral erythrodysesthesia syndrome has only rarely been described in the literature. We report on two female patients with breast cancer who on treatment with docetaxel developed acral erythrodysesthesia syndrome. It presented as bizarrely shaped, burning skin reactions at their hands and feet. Histology of skin biopsies revealed microscopic damages to the eccrine sweat glands in both patients. Skin patch testing with docetaxel was negative. None of the reports dealing with side effects of docetaxel chemotherapy has described acral erythrodysesthesia syndrome with the histologic features of syringo-squamous metaplasia and eccrine neutrophilic hidradenitis. We propose here that these characteristic histologic features are essential in the differentiation from fixed drug eruption and localized graft-versus-host disease.

Role of postoperative radiotherapy in the management of Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a high potential of locoregional relapse after surgery alone. This report is an update of our experience in the treatment of MCC. From January 1990 to May 2000, 31 patients with MCC, 13 men and 18 women aged between 34 and 92 years, were treated at the University of Cologne, Germany. Primary tumor sites were in the head and neck region in 13 patients, limbs in 13, and trunk in 5. The tumors were stage I in 26 of 31 patients, stage II in 4 of 31 and stage III in 1 of 31. Treatment included surgery alone in 14 of 31 patients, adjuvant postoperative radiotherapy in 16 of 31 patients, 1 of them had incomplete surgery, and definitive radiotherapy in 1 of 31 patients (stage III). Median overall survival (OS) after first diagnosis was 32 months (95% confidence interval: 0-75 months) with a 3-year OS rate of 47% (95% CI: 25-69%). Six of 31 patients relapsed locally after a median of 4 months, 10 of 31 patients developed regional node metastases, and 7 of 31 patients distant metastases. Nine patients died as a direct result of MCC. Locoregional control and disease-free survival were significantly improved in the group with postoperative radiotherapy (p = 0.023). Uni- and multivariate analysis revealed that head and neck location of the tumor and the lack of postoperative radiotherapy are unfavorable prognostic factors. Postoperative radiotherapy to the primary tumor region and the regional lymphatics is effective in the prevention of locoregional recurrence. Prospective clinical trials should be performed to confirm these observations.