Collapsing glomerulopathy in collagen vascular-like disease.

OBJECTIVE: Collapsing glomerulopathy (CG) is a podocytopathy that is usually associated with human immunodeficiency virus (HIV) and parvovirus B19 infections. CG has been reported in association with definite collagen vascular diseases, mainly systemic lupus erythematosus (SLE). There are a few case reports in the nephrology literature of patients with CG and marked serological abnormalities who do not have sufficient clinical findings to diagnose definite collagen vascular disease. We wish to expand the spectrum of rheumatologic disease that accompanies CG. We describe four patients with CG and collagen vascular-like disease and compare these with 14 similar cases reported in the medical literature. METHODS: Case reports of four new patients with CG and collagen vascular-like disease are presented. We performed a systematic literature review to find all other cases and construct a profile of patients with CG and collagen vascular-like disease. RESULTS: All patients had a similar mode of presentation with severe nephrotic range proteinuria and renal insufficiency resistant to steroids and usual immunomodulatory therapy. All patients had positive antinuclear antibodies (ANA) as well as other marked serological abnormalities but few if any clinical findings that would allow for a definitive diagnosis of a specific collagen vascular disease. Almost all patients became dialysis dependent. Mycophenolate mofetil (MMF) may possibly be a therapeutic option. CONCLUSION: Rheumatologists may be asked to consult on patients with severe proteinuria and renal insufficiency in the presence of marked serological abnormalities but few clinical symptoms and should be aware of this podocytopathy.

Transcatheter aortic valve replacement for advanced valvular disease in active SLE and APS.

Valvular heart disease is a relatively common finding in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), sometimes necessitating valve surgery. Valve replacement may result in significant early and late morbidity and mortality. Surgical risks are even greater when co-morbid conditions including active SLE and renal involvement are present. This is the first report of the successful use of transcatheter aortic valve replacement (TAVR) for severe critical aortic stenosis in a patient with active SLE, renal failure and APS. TAVR may represent an additional, safer, approach to cardiac valve replacement in appropriately selected patients particularly where surgical risk is high and active disease present.

Marked inflammation in catastrophic longitudinal myelitis associated with systemic lupus erythematosus.

Catastrophic longitudinal myelitis is an extremely rare neurologic manifestation of collagen vascular disease, described heretofore in 11 cases of SLE and 1 of Sjogren's Syndrome. This report documents markedly abnormal and worsening CSF findings on sequential CSF examinations over a period of three days (WBC >1500 cells/microL, >80% neutrophils, markedly elevated protein, and extremely low glucose levels) in the absence of infection. These abnormalities cleared rapidly with institution of immunosuppressive therapy so that a third CSF exam done within three days revealed almost complete normalization of CSF values. These findings suggest that in some cases of CLM a strong inflammatory component may be present, while in others, other pathogenic factors may predominate.

Treatment with sildenafil for the healing of refractory skin ulcerations in the antiphospholipid syndrome.

Nonhealing skin ulceration is a cutaneous manifestation of the antiphospholipid syndrome (APS) and is associated with thrombosis of small dermal vessels. Numerous therapies have been described but are either ineffective or require a prolonged course of treatment with potential complications. We describe the efficacy of sildenafil, a phosphodiesterase inhibitor, in the treatments of such ulcers.

Antibodies to beta 2-glycoprotein I and cardiolipin with symptoms suggestive of systemic lupus erythematosus in parvovirus B19 infection.

Parvovirus B 19 infection may mimic systemic lupus erythematosus (SLE) in its clinical presentation. Serological abnormalities during acute infection have been reported, including positive antinuclear antibodies and anti-doublestranded DNA antibodies. We describe a patient who, in addition to the clinical and laboratory findings suggestive of SLE, was found to have antibodies to cardiolipin and beta2 glycoprotein I. The symptoms resolved and the antibodies disappeared over a 9 month period. This report highlights the striking similarity between SLE and parvovirus B19 infection and the potential difficulty in distinguishing between the diseases.

Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment.

OBJECTIVE: To describe clinical manifestations, laboratory findings, and treatment of patients with the antiphospholipid syndrome (APS) who develop diffuse alveolar hemorrhage. METHODS: Diffuse alveolar hemorrhage is an occasionally reported manifestation of the APS. The diagnosis, however, may be overlooked or manifestations attributed to another disease process. Seven episodes in 5 patients with primary APS were identified and retrospectively reviewed for presenting symptoms and signs, laboratory findings, and response to treatment. RESULTS: The severity of the condition varies, and diffuse alveolar hemorrhage may be the initial manifestation of APS. Patients may present with symptoms ranging from cough, dyspnea, and fever with or without hemoptysis, to symptoms of acute respiratory failure. Hypoxemia and anemia are usually present. Other causes need to be excluded. Bronchoscopy and bronchoalveolar lavage with or without biopsy often aid in confirming the diagnosis. The pathologic abnormality appears to be microvascular thrombosis with or without capillaritis. Treatment with corticosteroids usually leads to marked improvement. CONCLUSION: Patients with APS may present with diffuse alveolar hemorrhage resulting in mild to life threatening symptoms. Prompt and thorough evaluation to confirm the diagnosis and treatment with corticosteroids usually leads to rapid improvement. The clinical setting will dictate whether other therapies such as immunosuppressive agents or intravenous immunoglobulin are required.

Calciphylaxis: a not-so-rare pseudovasculitis syndrome.

The assessment of any patient for possible vasculitis includes a thorough evaluation for other conditions that mimic vasculitis, particularly those in which corticosteroid and immunosuppressive treatment may be more harmful than beneficial. Calciphylaxis, which may be more common than previously recognized, is a syndrome associated with the development of painful skin nodules, often in a livedo reticularis pattern, skin necrosis and ulceration, myalgias, and elevated creatine kinase levels. Usually found in patients with chronic renal failure, the pathology is a distinctive mural calcification of small blood vessels. An incisional skin biopsy will reveal histologic findings of calcification within the media of small dermal blood vessels with superimposed intimal fibroblastic proliferation, causing marked luminal narrowing. Muscle biopsy specimens may also demonstrate calcium deposits within the walls of small perimysial vessels with intimal proliferation. Correction of calcium phosphate product, meticulous wound care, debridement if needed, and antibiotic therapy are essential, but the disease is associated with a high degree of morbidity and mortality. A parathyroidectomy may be beneficial. It has been suggested that corticosteroids and immunosuppressive agents may aggravate the condition. Awareness of this syndrome by rheumatologists will lead to proper diagnosis and treatment.

Digital necrosis in acquired immune deficiency syndrome vasculopathy treated with recombinant tissue plasminogen activator.

Widespread digital ischemic changes and gangrene of the hands and feet is an uncommon but dramatic presentation in patients with human immunodeficiency virus (HIV) infection. We describe a patient in whom these clinical findings were associated with elevated serum endothelin levels. Because endothelin may affect the fibrinolytic system, we elected to treat with tissue plasminogen activator (tPA), which resulted in salvage of tissue of the fingers and toes. Patients with HIV infection with widespread ischemic necrosis and gangrene may require treatment with corticosteroids (in the event of possible vasculitis), thrombolytic agents (for the thrombotic component), or both, unless there are contraindications to either.

Oral administration of an easily prepared solution of injectable methotrexate diluted in water: A comparison of serum concentrations vs methotrexate tablets and clinical utility.

OBJECTIVE: To investigate whether the injectable formulation of methotrexate (MTX) given as an easily prepared oral solution of MTX diluted in water results in serum concentrations similar to those obtained with MTX tablets; to describe an easy and safe method of dispensing the drug. METHODS: Six patients (5 women, 1 man) with rheumatoid arthritis were given 10 mg of liquid MTX orally. The liquid was prepared by diluting 0.4 ml of the injectable formulation of MTX (50 mg/2 ml) in 8 ounces of water. One to 2 weeks later these patients were given 10 mg of MTX in the tablet form. MTX serum concentrations were determined using a fluorescence polarization immunoassay. The area under the concentration vs time curve (AUC), maximum concentration (Cmax) and the time to reach maximum concentration (tmax) were determined from the resulting concentration vs time curves. RESULTS: There was no statistical difference in the variables measured (AUC, Cmax, tmax), demonstrating comparable concentrations with these 2 methods of MTX administration. Patients found the medication easy to administer, potential hazards with the use of needles were avoided, and the cost of the drug was greatly decreased. CONCLUSION: The administrator of this easily prepared MTX solution is an alternative to the conventional administration of MTX tables, and may be of particular benefit in patients with financial limitations.

Complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs.

OBJECTIVE: Many patients with chronic disease use alternative therapies. Our objective was to investigate complications resulting from the use of Chinese herbal medications containing undeclared prescription drugs, and to analyze these pills. METHODS: Medical records of 5 patients with complications were reviewed. Pills from symptomatic and asymptomatic individuals were analyzed for possible content of undeclared prescription drugs. RESULTS: All pills analyzed contained mefenamic acid and diazepam. Complications related to the presence of these substances included, among others, massive gastrointestinal bleeding. CONCLUSION: Chinese herbal medications may contain undeclared prescription drugs including nonsteroidal antiinflammatory drugs and benzodiazepines.

Systemic therapy with fibrinolytic agents and heparin for recalcitrant nonhealing cutaneous ulcer in the antiphospholipid syndrome.

Skin ulceration is a cutaneous manifestation of the antiphospholipid syndrome (APS) and is associated with thrombosis of small dermal vessels. Numerous therapeutic agents have been used but are often ineffective. We describe the efficacy of heparin and fibrinolytic agents [urokinase and tissue plasminogen activator (tPA)] in the treatment of longstanding nonhealing cutaneous ulcers. In one patient, heparin plus low dose tPA resulted in healing. In another patient, treatment first with urokinase and heparin, and subsequently with tPA alone, resulted in healing. When the ulcer recurred secondary to severe peripheral edema, tPA plus heparin led to complete resolution of the ulcer. This suggests that fibrinolytic therapy and/or heparin may be useful in other recurrent thrombotic manifestations of the APS as well. However, it must be emphatically stressed that since life threatening adverse reactions can occur secondary to hemorrhage, this treatment should be undertaken only after extensive evaluation and close monitoring of the coagulation status.

Pulmonary capillaritis, alveolar hemorrhage, and recurrent microvascular thrombosis in primary antiphospholipid syndrome.

Pulmonary manifestations of the antiphospholipid syndrome (APS) include pulmonary hypertension, pulmonary embolism, and in patients with the catastrophic APS, respiratory insufficiency associated with diffuse pulmonary infiltrates. There are few descriptions of pathological findings associated with these pulmonary complications. We document pulmonary capillaritis, recurrent microvascular thrombosis and alveolar hemorrhage in patients with APS. These patients have a wide spectrum of clinical presentations, ranging from recurrent episodes of fever, minimal hemoptysis, and mild dyspnea, to respiratory insufficiency requiring mechanical ventilation. Pulmonary involvement can occur alone or simultaneously with other manifestations of APS and may range from mild to severe. Pulmonary capillaritis and alveolar hemorrhage are complications of APS, and whether they are causally related to recurrent thromboembolism and pulmonary hypertension remains undetermined.

Massive soft tissue calcification causing complete loss of extensor tendon function in renal failure.

Extraskeletal soft tissue calcifications occur commonly in patients with uremia receiving dialysis. Rarely, a large tumoral calcinosis-like mass may develop. A patient receiving chronic ambulatory peritoneal dialysis for only 7 months developed a tumoral calcinosis-like mass that encased the extensor tendons of his wrist with loss of extensor tendon function, initially suggesting extensor tendon rupture. Surgical debridement restored tendon function. Tumoral calcinosis-like lesions are uncommon, but may cause limitation of joint movement, pain or ulceration through the skin. Measures aimed at controlling factors contributing to soft tissue calcification should be undertaken in any event whether surgery is required or not.

Intracardiac mural thrombus mimicking atrial myxoma in the antiphospholipid syndrome.

A wide spectrum of cardiac involvement including valvular lesions, myocardial infarction and myocardial dysfunction has been reported in patients with antiphospholipid antibodies (aPL), suggesting that cardiac manifestations may be part of the antiphospholipid syndrome (APS). We describe 3 patients (2 with primary APS and one with APS and SLE) who were found to have right atrial masses by echocardiography (transthoracic and/or transesophageal) and/or angiography, which were felt preoperatively to be atrial myxomata. Pathological examination of resected material showed only organized thrombus with calcification. We describe outcome 12 months to 7 years after resection of thrombus and document possible recurrence in one patient after 7 years. Intracardiac mural thrombus may be an additional cardiac manifestation of the APS, and presents considerable diagnostic confusion in its differentiation from atrial myxomata.

Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use.

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.

Eosinophilia-myalgia syndrome associated with L-tryptophan use.

The eosinophilia-myalgia syndrome associated with the use of oral preparations of the amino acid L-tryptophan was recognized in late 1989. We describe the clinical and laboratory manifestations, pathological findings and early clinical course of 20 patients with the eosinophilia-myalgia syndrome. Prominent clinical findings included severe myalgias limiting function, fatigue, rashes, edema and weight gain, weight loss, muscle weakness and shortness of breath. Laboratory findings included eosinophilia (often marked), normal erythrocyte sedimentation rate, and elevated aldolase with normal or low creatine kinase values. On biopsy fascial inflammation was always seen consisting of lymphocytes, histiocytes and eosinophils in a perivascular distribution. Invasion of the vascular wall by lymphocytes was seen in 20%. Capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25% of cases. Two patients improved with no therapy. Ten patients responded to therapy with prednisone alone. Three patients have had progressive disease and one of these died. The relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed.

Microangiopathy in the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome associated with the ingestion of L-tryptophan was recognized in late 1989. We describe our pathologic study of skin, fascial, and muscle biopsies from 21 patients evaluated by light microscopy, histochemistry, and electron microscopy. A perivascular, lymphocytic infiltrate with eosinophils was present in the dermis, fascia, and skeletal muscle. Lymphocytic infiltration of arteries and arterioles was seen. Ultrastructurally, capillary and arteriolar endothelial cell thickening and necrosis was present. This microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome.