Vasculitis confined to the calves. Report of a case

Polyarteritis nodosa is a systemic disease of which limited forms have been reported, with the most common involving the skin. Only 13 cases with lesions confined to the calves have been reported to date. We report a new case.     

Treatment of systemic vasculitis

Progress in the treatment of systemic vasculitis have permitted a decrease of mortality but with an increase in iatrogenic morbidity. Steroids remain the cornerstone of the treatment but precise modalities and other concomitant treatments are depending upon the type of vasculitis. In most cases, systemic vasculitis are primary and the treatment, although important, is symptomatic. However, in some cases such as hepatitis B virus-induced polyarteritis nodosa or hepatitis C virus-induced cryoglobulinemia, the treatment can be etiologic and is directed against the antigen responsible for the systemic vasculitis. In the future, a better understanding of pathological mechanisms, particularly of etiologic factors, and new treatment such as monoclonal antibodies should increase the prognosis of systemic vasculitis.     

Mortality and risk of cancer in systemic connective tissue diseases

The systemic connective tissue diseases represent a broad spectrum of multiorgan disorders. This report reviews our current knowledge of mortality and the risk of cancer in these diseases. The relationship between clinical manifestations and reduced survival in systemic sclerosis, systemic lupus erythematosus and polyarteritis nodosa is addressed in detail. Moreover, we outline the increased risks of cancer in dermatomyositis and lymphoma in primary Sj?gren's syndrome, as well as cancer of the bladder in patients with Wegener's granulomatosis who have been treated with cyclophosphamide. Finally, the conflicting results regarding mortality in temporal arteritis are discussed.     

Steroid and non-steroidal anti-inflammatory drug therapy of vasculitis

Before corticosteroids were used in the treatment of the systemic necrotizing vasculitides of the polyarteritis nodosa, the disease almost always progressed with variable degree of fulminance leading to death. The use of corticosteroids improves the 5-year survival. The most dramatic break-through in the therapeutic approach to the vasculitides has been clinical experience with cyclophosphamides in treating Wegener's granulomatosis. With this therapeutic regimen, Wegener's granulomatosis can now be considered a curable disease, if treated early and appropriately with therapeutic regimen. These therapeutic strategy can be extended to that of polyarteritis nodosa group of vasculitides. Now, it is clear that cyclophosphamide, either alone or in combination with pre-existing corticosteroid therapy, can effect a dramatic response if instituted early in the course of the disease process. With the advent of deeper insight as to immuno-pathogenesis and pathophysiologic mechanism, the striking therapeutic success can be expected in near future.     

Small vessel vasculitis and vasculitis confined to skin

Cutaneous vasculitis is a heterogeneous group of disorders, which can be confined to the skin or may be part of an associated systemic disease. Various aetiological agents as well as conditions that mimic skin vasculitis, usually present with similar clinical features; mainly palpable purpura. The skin biopsies usually show leukocytoclastic vasculitis. This poses a great diagnositc and therapeutic challenge for the physician. The aetiologies, clinical features, diagnosis and treatment modalities for each form (drugs, infections, malignancies, systemic vasculitides, connective tissue disorders. Sch?nlein-Henoch purpura, cryoglobulinaemia, cutaneous periarteritis nodosa, livedoid vasculitis, erythema elevatum diutinum and urticarial vasculitis) are reviewed.     

Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections

BACKGROUND: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis associated with multi-organ involvement. Cutaneous polyarteritis nodosa is purported to be a more benign form of this disorder with involvement limited to the skin. METHODS: The identification of a female patient from childhood to adulthood documenting repeated episodes of cutaneous polyarteritis nodosa following bouts of recurrent streptococcal pharyngitis. RESULTS: Repeated bouts of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin changes and clinical presentation, and confirmed by therapeutic management. CONCLUSIONS: Various infectious and non-infectious conditions have been linked both to the initiation and relapse of this disease. We describe a patient with recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20 years with each episode appearing to be linked to a prior streptococcal infection.     

Thalidomide increases both REM and stage 3-4 sleep in human adults: a preliminary study

OBJECTIVE: Methotrexate has been documented to accumulate in pleural effusions and ascitic fluid, resulting in severe local and systemic toxicity. In the following case report, we publish results of intraoperative measurements of methotrexate levels in serum and an ovarian cyst and attempt to determine if ovarian cysts similarly act as a depot for methotrexate. METHODS: After determining intraoperative measurements of serum and ovarian cystic levels of methotrexate, we compared demonstrated pharmacokinetics to those expected by using pharmacokinetic systems analysis software. RESULTS: Intraoperative measurement of methotrexate levels on day 3 of a 5-day methotrexate regimen revealed a serum methotrexate concentration of 1.6 x 10(-7) M and a concentration of 3.1 x 10(-7) M within the 166.4 ml ovarian cyst. CONCLUSIONS: The measured levels demonstrate that methotrexate is sequestered within an ovarian cyst resulting in higher local drug levels. Our pharmacokinetic analysis suggests that methotrexate doses less than 100 mg/m2 can be safely administered to patients with small ovarian cysts. However, computed simulations support the possibility of local and systemic toxicity arising from large ovarian cysts when using high doses of methotrexate.     

Inferior suprarenal artery aneurysm in polyarteritis nodosa

A 16-year-old boy with the complaints of fever, abdominal pain, arthralgia and hypertension was found to have polyarteritis nodosa. Selective renal angiography disclosed a 5-mm microaneurysm of the right inferior suprarenal artery, which has not been previously reported in polyarteritis nodosa. Aside from the diagnostic view-point, some of the perirenal and retroperitoneal hemorrhages of unknown origin seen in polyarteritis nodosa might be due to the rupture of suprarenal artery aneurysms.     

Salpingitis isthmica nodosa: results of transcervical fluoroscopic catheter recanalization

OBJECTIVE: To investigate the role of transcervical tubal catheterization in diagnosis and treatment of proximal tubal obstruction associated with salpingitis isthmica nodosa. DESIGN: Retrospective case study. SETTING: University hospital and outpatient radiology practice. PATIENTS: Fifty-two women with proximal tubal obstruction associated with salpingitis isthmica nodosa. INTERVENTION: Selective salpingography and catheter recanalization using fluoroscopic guidance. MAIN OUTCOME MEASURES: The number of tubes visualized to the fimbria as a percentage of the tubes with proximal tubal obstruction on the initial hysterosalpingogram was determined as a measure of diagnostic efficacy. To evaluate the treatment potential of catheter recanalization, the patients were grouped according to tubal status at the conclusion of the procedure and subsequent pregnancies were evaluated. RESULTS: Forty-seven of 65 tubes (72%) with proximal tubal obstruction were recanalized successfully. Among the 19 women who were able to conceive only via a recanalized salpingitis isthmica nodosa tube, there were 6 live births (32%) and two tubal pregnancies (10%). CONCLUSION: Selective salpingography allows complete tubal diagnosis in almost three fourths of patients with proximal tubal obstruction and salpingitis isthmica nodosa. The radiographic diagnosis of salpingitis isthmica nodosa may be pressure dependent. Intrauterine pregnancies occur via recanalized salpingitis isthmica nodosa tubes, therefore catheter recanalization may be attempted before tubal microsurgery or IVF in patients with proximal tubal obstruction and associated salpingitis isthmica nodosa.     

Threshold of the soleus muscle H-reflex is less sensitive to the change in excitability of the motoneuron pool during plantarflexion or dorsiflexion in humans

Pulmonary vasculitides require major therapeutic regimens which, though symptomatic, are often effective. Corticosteroids have greatly changed the prognosis of most of these vasculitides, particularly polyarteritis nodosa and the Churg and Strauss syndrome. Cyclophosphamide must be added for Wegener's granulomatosis although the route of administration is still under discussion. Plasma exchanges are rarely indicated. Other treatments for Wegener's granulomatosis including combined trimethoprim-sulfamethoxazole in limited forms and methotrexate in sub-acute systemic forms are currently under study. A better understanding of the underlying mechanisms, including the role of antineutrophil cytoplasmic antibodies, and especially the identification of the causative factors will lead to an aetiologic treatment still unknown today.     

Embolization of a ruptured aneurysm in classic polyarteritis nodosa presenting as perirenal hematoma

A 26-year-old man was admitted with abdominal pain, anemia, and hypertension. Ultrasonography and computed tomography revealed a perirenal hematoma. Soon after admission, the patient went into shock, and emergency angiography was performed. Two active bleeding sites were found in the left kidney and were successfully embolized. Also, multiple aneurysms, consistent with the diagnosis of classic polyarteritis nodosa, were seen. After treatment was initiated, the patient recovered fully. When a spontaneous perirenal hematoma is a presenting symptom of classic polyarteritis nodosa, a delay in making the right diagnosis is likely to occur. Angiography not only may provide a quick diagnosis, but it can also be used to perform therapeutic embolization. In patients with classic polyarteritis nodosa and hemorrhage from a ruptured aneurysm, angiography may be a therapeutic alternative to surgery.     

Intrahepatic bile duct injury and nodular regenerative hyperplasia of the liver in a patient with polyarteritis nodosa

Although involvement of the hepatic vasculature in patients with polyarteritis nodosa is not unusual, biliary manifestations are very rare. We describe a patient with polyarteritis nodosa presenting with a febrile cholestatic anicteric syndrome. Histological examination of the liver revealed necrotizing arteritis of small hepatic arteries associated with significant lesions of intrahepatic bile ducts of the sclerosing cholangitis type, i.e. fibrous collar around the ducts, periductal inflammation and ductal proliferation. Concomitant nodular regenerative hyperplasia was found, a condition which has rarely been described in association with polyarteritis nodosa. We think that hepatic arteritis compromising arterial blood flow to the liver was responsible for the most likely ischemic nature of the bile duct injury and the nodular regenerative hyperplasia seen in our patient.     

Association of acute pericarditis and acute renal insufficiency: causes and prognosis

OBJECTIVE: To assess the etiologic diagnoses and outcome of acute pericardial effusion associated to acute renal renal failure. PATIENTS AND METHODS: A retrospective study from 1978 to 1996 in a 10 bed medical/surgical intensive care unit included 11 patients who have an acute pericardial effusion associated with an acute renal failure. RESULTS: Etiological diagnoses were systemic lupus with extracapillary glomerulonephritis (n = 2), systemic fibrosis with obstructive renal failure (n = 2), anticoagulation accident with hemodynamic renal failure (n = 2), lung adenocarcinoma (n = 2), adenocarcinoma of undetermined origin (n = 1), systemic polyarteritis nodosa (n = 1), and Wegener granulomatosis (n = 1). Intensive care unit deaths was 4, including 2 cases of neoplasic origin. DISCUSSION: Despite infection or malignancy being claimed as the leading causes of acute pericardial effusion, when associated to acute renal failure other etiologic diagnoses, such connectivite tissue disease or vasculitis, must be evoked that prompt specific treatment and could prevent unfavorable evolution. Neoplasic causes were characterised by receiving pericardial effusion and a high mortality rate.     

Severe preeclampsia superimposed on polyarteritis nodosa

A patient with a history of drug abuse and histologically diagnosed hepatitis B-related polyarteritis nodosa was admitted for severe hypertension. After a cesarean section because of worsening of her clinical status with severe proteinuria and edema, she improved dramatically. No sign of acute polyarteritis nodosa occurred.     

Churg-Strauss syndrome. Personal caseload and review of the literature

Churg-Strauss syndrome (CSS) is a disease characterised by hypereosinophilia and systemic vasculitis occurring in patients with asthma and allergic rhinitis. In the course of CSS three phases may be distinguished. The prodromal phase, which may persist for many years, consists of allergic disease. The second phase is characterised by peripheral blood eosinophilia and eosinophilic tissue infiltrates that produce a clinical picture diagnosed as Loeffler's syndrome, chronic eosinophilic pneumonia or eosinophilic gastroenteritis. The third phase is dominated by systemic vasculitis in which skin, cardiovascular system, gastrointestinal tract and peripheral nervous system are frequently involved. Renal disease in CSS is less common and generally less severe than that classical polyarteritis nodosa and Wegener's granulomatosis. Genitourinary tract may be involved, too. In the postvaculitic phase, allergic rhinitis and asthma usually persist and clinical picture is characterised by the consequences of the vasculitic illness, most commonly in form of neuropathy and hypertension. The pathogenesis of CSS is unknown but its association with asthma and allergic rhinitis may indicate an abnormal immune reactivity. The recently reported association with antineutrophil cytoplasmic antibodies with antimyeloperoxidase specificity may suggest a their role in the pathogenesis of the disease. An important role may be played by eosinophils, too. The main therapy is that with corticosteroids, possibly in association with immunosuppressive drugs.     

Serum ELAM-1 is increased in vasculitis, scleroderma, and systemic lupus erythematosus

OBJECTIVE: To investigate the state of endothelial cell activation in vasculitis, scleroderma, and systemic lupus erythematosus (SLE). METHODS: We used a sandwich ELISA to quantitate a soluble form of endothelial leukocyte adhesion molecule-1 (sELAM) in serum. RESULTS: sELAM was detected in serum from healthy individuals (mean 0.92 ng/ml). Levels were significantly higher in patients with giant cell arteritis (mean 2.04 ng/ml), polyarteritis nodosa (mean 2.08 ng/ml), scleroderma (mean 2.27 ng/ml), and SLE (mean 3.93 ng/ml). Elevated values were present in patients with both active and inactive disease. sELAM levels of > 3 ng/ml identified most patients with recent onset or active disease. CONCLUSION: Our findings may reflect a low degree of endothelial cell activation in healthy persons that is increased in inflammatory diseases involving blood vessels. Elevated serum sELAM levels may reflect ongoing inflammatory processes in these diseases.     

Microangiopathic hemolytic anemia with metastatic adenocarcinoma: response to chemotherapy

Microangiopathic hemolytic anemia developed in two patients with metastatic malignancy, one with primary carcinoma of the colon and the other with ovarian carcinoma. There was no evidence of consumptive coagulopathy except severe thrombocytolysis in one patient. Both patients improved remarkably after chemotherapy. The colonic carcinoma responded to 5-fluorouracil delivered into the hepatic artery, and the ovarian tumor to multiagent systemic therapy.     

Surgical reduction of "big eyes"

We report a case of central retinal vein occlusion (CRVO) in a young woman with polycystic ovarian syndrome (PCOS). CRVO in young patients is a rare condition, frequently associated with a severe underlying systemic disorder. This is the first report of CRVO associated with documented PCOS. We discuss the therapeutic dilemma.     

Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients

Cutaneous vasculitis (CV), a condition characterized by palpable purpura and nonspecific histopathologic findings, presents a diagnostic and therapeutic challenge because it may be a primary disorder or it may be a cutaneous manifestation of another entity, such as systemic necrotizing vasculitis, connective tissue disease, systemic bacterial infection, or malignancy. We studied 303 unselected patients (172 adults and 131 children) with CV to assess the disease associations and etiologic factors, to identify the frequency of primary and secondary CV in different age-groups, and to characterize features that help to distinguish between primary and secondary CV. Of the 131 children, 130 had primary CV: Henoch-Sch?nlein purpura (HSP) in 116 and hypersensitivity vasculitis (HV) in 14. In contrast, of the 172 adults, only 120 had primary CV: HSP in 39, HV in 70, and essential mixed cryoglobulinemia in 11. CV was a manifestation of systemic necrotizing vasculitis in 23 adults (polyarteritis nodosa in 17, Wegener granulomatosis in 4, and Churg-Strauss syndrome in 2). CV was secondary to other processes in 29 adults: in 20 patients CV was associated with connective tissue disease or another autoimmune or rheumatic disease, in 5 patients CV was a manifestation of severe bacterial infection, especially bacterial endocarditis (4 cases), and in the other 4 patients CV was the presenting symptom of an underlying malignancy. The patients for whom CV was a manifestation of systemic necrotizing vasculitis or secondary to a connective tissue disease, severe bacterial infection, or malignancy had clinical and laboratory data suggestive of the associated disorder. The clinical picture and outcome of primary CV in both children and adults were benign. By contrast, the prognosis of patients with CV in the context of systemic necrotizing vasculitis or secondary to other entities depended on the primary process. Given the different disease association in children and adults, we propose a simple diagnostic workup in children with CV. By contrast the diagnostic approach in adults with CV should be more cautious and the workup more extensive. The early differentiation between primary CV, secondary CV, and CV presenting as a symptom of systemic necrotizing vasculitis, especially in adults, is of paramount importance for an adequate diagnosis and appropriate treatment.     

Differential effects of indomethacin on the sheep ovary: prostaglandin biosynthesis, intracellular calcium, apoptosis, and ovulation

Cells of the apical wall of the dominant follicle and contiguous ovarian surface epithelium become apoptotic with the approach of ovulation in the sheep. It was hypothesized that indomethacin, an established inhibitor of prostaglandin biosynthesis and ovulation, would protect apical ovarian cells from programmed death. The anovulatory potencies of two systemic doses of indomethacin (200 and 800 mg) were tested in gonadotropin-stimulated ewes. A complete blockade of ovulation occurred at the higher dose of indomethacin. Ovulation was not inhibited by 200 mg indomethacin. Both doses of drug suppressed follicular prostaglandin production below pregonadotropin levels. Immunofluorescence detection of digoxigenin end-labeled (fragmented) DNA was used as a marker of apoptosis among ovarian surface epithelial and granulosa cells recovered from the optical hemisphere of preovulatory ovine follicles. Cellular DNA fragmentation was averted in animals given 800 mg indomethacin, whereas apoptosis ensued after 200 mg. A sustained increase in cytosolic calcium is generally a prerequisite to apoptotic DNA fragmentation and cell death. Indeed, intracellular calcium, detected by fluorescence of fura-2, was elevated in ovarian cells of animals destined to ovulate (controls, 200 mg indomethacin) in comparison to (safeguarded) cells of anovulatory ewes (800 mg indomethacin). These observations provide circumstantial evidence that apical ovarian cell degeneration by calcium-mediated apoptosis is a determinant of follicular instability and rupture, but that these events are unrelated to the gonadotropin-induced rise in prostanoid production characteristic of preovulatory follicles.