Vojislav D. Vuzevski

Erythromelalgia Caused by Platelet-Mediated Arteriolar Inflammation and Thrombosis in Thrombocythemia

Erythromelalgia was the presenting symptom in 26 of 40 patients with thrombocythemia in its primary form or when associated with polycythemia vera. The localized painful burning, redness, and warm congestion in the extremities could be accurately documented with thermography. Skin punch biopsy samples taken from the affected areas showed typical arteriolar inflammation, fibromuscular intima proliferation, and thrombotic occlusions. Erythromelalgia often progressed to ischemic acrocyanosis or necrosis in toes or fingers. Complete relief of pain and restoration of microvascular circulation disturbances was obtained with the cyclo-oxygenase inhibitors aspirin and indomethacin, but not with sodium-salicylate or the platelet inhibitors dipyridamole, sulfinpyrazone, ticlopidine, and dazoxiben. The erythromelalgia was alleviated during busulfan-induced remissions of thrombocythemia and its recurrence coincided with relapsing thrombocythemia. These observations suggest a causal relationship between erythromelalgia and thrombocythemia, in which platelet-mediated inflammatory and occlusive arteriolar changes play a part in the etiology of erythromelalgia.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results

OBJECTIVES The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

Histopathology of erythromelalgia in thrombocythaemia.

Erythromelalgia always appears to be an expression of thrombocythaemia which may be provoked by intravascular platelet aggregation, because it is relieved by agents interfering with platelet prostaglandin synthesis. Biopsies were taken from affected areas 1–3 weeks after discontinuation of aspirin. At that time arteriolar changes were present: the endothelial cells were often swollen with large nuclei. Narrowing of the lumen occurred by proliferation of smooth muscle cells with vacuolisation and swelling of the cytoplasm and deposition of intercellular material. The internal elastic lamina appeared to be split between the proliferated cells. This gave rise to the appearances of fibromuscular intimal arteriolar proliferation which were often occluded by thrombi of differing age. Ultimately the arterioles become completely fibrosed. These vascular changes are restricted to arterioles, are partly reversible with aspirin treatment and seem to be a characteristic of erythromelalgia.

The effect of cigarette smoking on the survival of free vascularized and pedicled epigastric flaps in the rat

&NA; Microsurgeons suspect that cigarette smoking reduces the survival of free vascularized flaps and replantations, but this has never been proven. This experimental study investigates the effect of smoking on free‐flap survival. A fasciocutaneous epigastric flap was used in 30 rats as a free flap and in 30 rats as a pedicled flap. Of each group, 10 rats were smoked 6 weeks before and 2 weeks after surgery, 10 rats were smoked only 6 weeks before surgery, and 10 rats underwent the sham smoking procedure. Also, a distally based dorsal skin flap was cut in all rats, representing a random vascularized flap. Vitality and size of both flaps and patency of the vascular anastomoses were assessed 14 days after surgery. The epigastric flaps were monitored by laser Doppler flowmetry and thermometry during the experiment. Survival of the free vascularized epigastric flaps was significantly lower in smoking rats. All pedicled flaps except one survived. The epigastric flaps only necrosed or survived completely, exactly correlating to the patency of the vascular anastomoses. The mean surviving area of the dorsal flaps was best for nonsmoking rats, worse for only preoperatively smoking rats, and worst for preoperatively and postoperatively smoking rats. The differences were statistically significant. Postoperative laser Doppler flow differed significantly between surviving and dying flaps, affirming the value of laser Doppler flow monitoring in microvascular surgery. In conclusion, this study proves that smoking of cigarettes is detrimental to the survival of free vascularized flaps. (Plast. Reconstr. Surg. 97: 86, 1996.)

Primary cutaneous adenoid cystic carcinoma: case report, immunohistochemistry, and review of the literature

We report a case of primary cutaneous adenoid cystic carcinoma in a 75‐year‐old man. Electron microscopy revealed similar features to those previously described in adenoid cystic carcinomas of salivary gland origin: wide intercellular spaces, pseudocysts containing replicated basement membrane‐like material and true lumina lined by cytoplasmic membranes with numerous microvilli. Immunohistochemistry using antibodies to several cytoskeletal proteins (keratins and actin) indicated the presence of two epithelial tumour cell populations, one with the phenotype of myoepithelial cells, lining the pseudocysts and the periphery of the tumour fields, and another with the phenotype of acinar cells of the secretory coil of sweat glands. In addition, the tumour showed immunoreactivity for epithelial membrane antigen, but not carcinoembryonic antigen. A review of the literature on other cases of primary cutaneous adenoid cystic carcinoma showed that this tumour generally affects older patients with a female to male ratio of 4:1. The most common tumour site appears to be the scalp (40%), and the recurrence rate is 50%. Surgical treatment with extensive resection margins is recommended.

Idiopathic erythermalgia: a congenital disorder

Idiopathic erythermalgia during early childhood and adolescence is characterized by red, congested, burning pain of the lower extremities provoked by exercise or exposure to warmth. The clinical symptoms of idiopathic erythermalgia in a young woman and her mother are described. Histopathologic and immunofluorescence findings in biopsy specimens of affected areas of skin were consistent with a nonspecific inflammatory process. The condition was completely refractory to any treatment. Even the long-lasting relief of pain with one low dose of aspirin, which is a prerequisite for the diagnosis of thrombocytemic erythromelalgia, was lacking. Idiopathic erythermalgia appears to be a separate clinical entity and congenital disorder.

Verapamil-induced secondary erythermalgia

Summary A 59‐year‐old man developed red, swollen and warm feet accompanied by intermittent burning pain during treatment for cardiac failure and arrhythmias with several drugs including verapamil. The condition gradually worsened until there was persistent disabling burning pain and severe erythema and swelling of the feet. Aspirin and other analgesics were ineffective in relieving the discomfort. Histopathology of punch biopsies showed a mild perivascular mononuclear infiltrate and moderate perivascular oedema. Within 2 weeks of stopping verapamil the burning pain, erythema, and swelling of the feet had resolved. The clinical features and subsequent course are consistent with a diagnosis of erythermalgia secondary to verapamil.

Diffuse Cutaneous Mastocytosis Mimicking Staphylococcal Scalded-Skin Syndrome: Report of Three Cases

Abstract: Three cases of diffuse cutaneous mastocytosis (DCM) were at first incorrectly diagnosed as staphylococcal scalded‐skin syndrome. In the first patient, at age 1 day the disease was recognized promptly by simple techniques such as Dariers sign and Tzanck smear. Much delay in making the diagnosis occurred in the other two patients, however: almost 1 year and 15 years, respectively.

Expression of interferon‐gamma receptors and interferon‐gamma‐induced up‐regulation of intercellular adhesion molecule‐1 in basal cell carcinoma; decreased expression of IFN‐γR and shedding of ICAM‐1 as a means to escape immune surveillance

The peritumoural inflammatory infiltrate in basal cell carcinoma (BCC) of the skin consists mainly of T lymphocytes which hardly invade the tumour nests. The absence of intercellular adhesion molecule‐1 (ICAM‐1) on BCC cells may explain the lack of tumour‐infiltrating cells and the lack of an active cell‐mediated immune response in this tumour. In this study, the induction of ICAM‐1 was investigated in BCC biopsies using recombinant human interferon‐gamma (rHuIFN‐γ). The expression of interferon‐gamma receptors (IFN‐γR) in the biopsies was also investigated. The results showed that BCC cells expressed ICAM‐1 after incubation with rHuIFN‐γ, but to a lesser degree than normal epidermal cells. The levels of shed ICAM‐1 were significantly increased in the culture supernatants of tumour biopsies compared with those from normal skin biopsies, after culturing in the presence of rHuIFN‐γ. The expression of IFN‐γR was significantly decreased on the tumour cells compared with the overlying epidermis. The decreased expression of IFN‐γR on the tumour cells and the shedding of ICAM‐1 into the peritumoural stroma may be a plausible mechanism by which the tumour cells are protected against an active cell‐mediated immune response.

Cutaneous pathology in primary erythermalgia

Primary or idiopathic erythermalgia is characterized by recurrent, red, warm, and painful lower extremities. It arises at young age and persists throughout life because no treatment is available. We report the cutaneous pathology of affected skin lesions of three patients with primary erythermalgia. Biopsy specimens showed a mild perivascular mononuclear infiltrate, thickened blood vessel basement membranes, abundant perivascular edema, and moderate endothelial swelling. The thickened basal membrane of the blood vessels showed a laminar structure, and abundant perivascular edema and moderate endothelial cell swelling were evident. These histopathologic findings in primary erythermalgia appear to be nonspecific but allow diagnostic differentiation from erythromelalgia in which fibromuscular intimal proliferation and occlusive thrombi in the endarteriolar capillaries are apparent and from erythermalgia secondary to vasculitis. Histopathologic examination of affected skin lesions in patients with red, congested, warm, and painful burning extremities is a valuable tool in the diagnostic process.