Adel G. Fam

Efficacy and safety of desensitization to allopurinol following cutaneous reactions.

OBJECTIVE To evaluate the long-term efficacy and safety of slow oral desensitization in the management of patients with hyperuricemia and allopurinol-induced maculopapular eruptions. METHODS A retrospective evaluation of an oral desensitization regimen using gradual dosage-escalation of allopurinol in 32 patients (30 with gout and 2 with chronic lymphocytic leukemia) whose therapy was interrupted because of a pruritic cutaneous reaction to the drug. RESULTS Twenty-one men and 11 women with a mean age of 63 years (range 17-83 years), a mean serum urate level of 618 micromoles/liter (range 495-750) (or, mean 10.4 mg/dl [range 8.3-12.6]), and a mean serum creatinine level of 249 micromoles/liter (range 75-753) (or, mean 2.8 mg/dl [range 0.8-8.5]) were studied. Desensitization failed in 4 patients because of unmanageable recurrent rash. Twenty-eight patients completed the desensitization procedure to a target allopurinol dosage of 50-100 mg/day, 21 without deviation from the protocol for a mean of 30.5 days (range 21-56 days) and 7 requiring dosage adjustments because of a recurrent rash over 53.8 days (range 40-189 days). Seven of these 28 patients developed late cutaneous reactions 1-20 months postdesensitization, 4 responding to dosage modification and 3 discontinuing the drug. Twenty-five of the 32 patients (78%) continued to take allopurinol; their mean duration of followup was 32.6 months (range 3-92 months) and the mean postdesensitization serum urate level was 318 micromoles/liter (range 187-452) (or, mean 5.3 mg/dl [range 3.0-7.5]). CONCLUSION The study confirms the long-term efficacy and safety of slow oral desensitization to allopurinol in patients with maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate-lowering drugs. Although pruritic skin eruptions may recur both during and after desensitization, most of these cutaneous reactions can be managed by temporary withdrawal of allopurinol and dosage adjustment.

Gout in the elderly. Clinical presentation and treatment.

Gout in the elderly differs from classical gout found in middle-aged men in several respects: it has a more equal gender distribution, frequent polyarticular presentation with involvement of the joints of the upper extremities, fewer acute gouty episodes, a more indolent chronic clinical course, and an increased incidence of tophi. Long term diuretic use in patients with hypertension or congestive cardiac failure, renal insufficiency, prophylactic low dose aspirin (acetylsalicylic acid), and alcohol (ethanol) abuse (particularly by men) are factors associated with the development of hyperuricaemia and gout in the elderly.Extreme caution is necessary when prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute gouty arthritis in the elderly. NSAIDs with short plasma half-life (such as diclofenac and ketoprofen) are preferred, but these drugs are not recommended in patients with peptic ulcer disease, renal failure, uncontrolled hypertension or cardiac failure. Colchicine is poorly tolerated in the elderly and is best avoided. Intra-articular and systemic corticosteroids are increasingly being used for treating acute gouty flares in aged patients with medical disorders contraindicating NSAID therapy.Urate-lowering drugs are indicated for the treatment of hyperuricaemia and chronic gouty arthritis. Uricosuric drugs are poorly tolerated and the frequent presence of renal impairment in the elderly renders these drugs ineffective. Allopurinol is the urate-lowering drug of choice, but its use in the aged is associated with an increased incidence of both cutaneous and severe hypersensitivity reactions. To minimise this risk, allopurinol dose must be kept low. A starting dose of allopurinal 50 to 100mg on alternate days, to a maximum daily dose of about 100 to 300mg, based upon the patient’s creatinine clearance and serum urate level, is recommended. Asymptomatic hyperuricaemia is not an indication for long term urate-lowering therapy; the risks of drug toxicity often outweigh any benefit.

Kaposi's sarcoma complicating corticosteroid therapy for temporal arteritis

Combination immunosuppressive therapy, particularly in renal transplant recipients, is associated with a higher than expected risk of development of Kaposis sarcoma, In this report, cutaneous dissemination of Kaposis sarcoma occurred in a patient with temporal arteritis who was treated with corticosteroids. Reduction of the steroid dosage was followed by regression of the tumor. This sequence of events suggests a causal relationship between the evolution of the sarcoma and corticosteroid therapy. Although Kaposis sarcoma may complicate corticosteroid therapy alone, the incidence is considerably lower than in renal transplant recipients receiving combination immunosuppressive therapy. Considering the large number of patients with temporal arteritis who are treated with steroids and that this is the first report of its association with Kaposis sarcoma, it seems that other factors, perhaps genetic, might be important in the development of this neoplasm.

Neonatal Behçet's syndrome in an infant of a mother with the disease.

Behçets disease is reported in a newborn infant of a mother with the disease. The mother had recurrent orogenital ulcers, pustulonecrotic skin lesions, arthritis, thrombophlebitis, and colonic ulcers. Shortly after birth the infant presented with transient orogenital ulcerations and pustular cutaneous lesions. On healing, depressed scars developed which were very similar to those of the mother. The finding of circulating immune complexes in the mothers serum gives some support to the hypothesis that the infants transient illness was caused by transplacental passage of maternal antibodies.

Treating acute gouty arthritis with selective COX 2 inhibitors.

Few arthritides are as painful, incapacitating, and stressful as a severe attack of acute gout, pseudogout, or calcific periarthritis. Successful treatment of these acute microcrystalline events depends on early use of an effective and safe anti-inflammatory drug in full dosage. The sooner such treatment is started the more rapid and complete the response. Treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids including adrenocorticotrophic hormone.1 Although colchicine is traditionally rooted in the treatment of acute gout, in recent years its use has declined steadily.1 Its drawbacks include slow onset of action, narrow ratio of benefit to toxicity, and reduced efficacy when used more than 24 hours after the an attack begins. Colchicine (0.6 mg orally every 2 hours, up to 4-6 mg/day) is now reserved for patients without renal, hepatic, or bone marrow disease, in whom the more effective NSAIDs are contraindicated or poorly tolerated. Intravenous colchicine is best avoided given its potential for serious toxicity, which potentially can result in myelosuppression, hepatic necrosis, renal failure, hypotension, seizures, and death. Intra-articular corticosteroids (for example, methylprednisolone acetate 5-25 mg per joint), systemic corticosteroids (oral prednisone 20 mg/day tapered off over 4-10 days, or intramuscular triamcinolone hexacetonide 60 mg/day, repeated …

Recent advances in the management of adult myositis

Standard drug therapy of adult polymyositis, dermatomyositis and inclusion body myositis includes high-dose corticosteroids and cytotoxic drugs (methotrexate, azathioprine (AZA) and cyclophosphamide). Recent data are in favour of the early introduction of a cytotoxic or immunomodulating drug in addition to corticosteroid therapy. In patients with corticosteroid- and cytotoxic-resistant myositis, promising novel approaches to management include: iv. megadose pulse methylprednisolone combined with cytotoxic drugs, combination therapy with both methotrexate and AZA, cyclosporin, tacrolimus, fludarabine and iv. immunoglobulin (IVIG). Recent advances in the understanding of the role of cytokines and complement, in the pathogenesis of myositis, have led to preliminary therapeutic trials of three biological agents: etanercept, infliximab and anti-C5 monoclonal antibody.

Multiple-crystal acute polyarthritis

A patient with acute polyarthritis due to crystal-positive simultaneous gout and pseudogout affecting different joints is described. The case emphasises the importance of aspirating more than one involved joint and carefully searching for crystals in patients with acute arthritis involving 2 or more joints, particular those in whom the diagnosis of multiple crystalline joint disease is considered.

Herpes Zoster During Gold Therapy

Excerpt To the editor: Studies describing the various cutaneous reactions associated with gold therapy for rheumatoid arthritis have not included herpes zoster (1). Known precipitants of zoster inc...

Less Common Arthropathies

Musculoskeletal manifestions of hematologic and malignant disorders are reviewed in this chapter. A list of these conditions is shown in Table 25A-1.