Hydroxychloroquine Sulfate Research Articles

Resistant discoid lupus erythematosus of palms and soles: Successful treatment with azathioprine

We present the case of two patients with an unusual form of discoid lupus erythematosus that was confined almost exclusively to the palms and soles. In both patients this form of discoid lupus erythematosus did not respond to conventional therapies, which included topical steroids, intralesional steroids, prednisone, quinacrine hydrochloride, hydroxychloroquine sulfate, colchicine, and dapsone. Both patients were then treated with azathioprine. One patient dramatically improved with azathioprine, worsened each time the azathioprine was stopped or reduced, and responded again to the reinstitution of therapy. The other patient began taking azathioprine 8 months ago and has also experienced relief of her symptoms. These cases suggest that discoid lupus erythematosus principally involving the palms and soles is difficult to treat with conventional medication and that azathioprine, which appears to be useful, should be tried after the failure of other therapies.

Diphosphonate Bone Scans in Patients With Polyarthralgias

Early detection of inflammatory arthropathy is notoriously difficult with standard radiographic techniques. We therefore assessed bone turnover with technetium Tc 99m medronate in 16 patients with persistent polyarthralgias who had no clinical synovitis, normal radiographs, and nondiagnostic results from laboratory evaluations. Abnormal scans were found in 11 of 16; five were unremarkable. Scan abnormality corresponded with symptomatic joints (11 of 11 patients). These 11 patients had normal test results for rheumatoid factor, antinuclear antibody, and HLA-B27. Patients with abnormal scans were treated with nonsteroidal antiinflammatory drugs or analgesics (11 of 11), hydroxychloroquine sulfate (four), or gold salts (one), with improvement (nine of 11); patients with normal scans (five of five) were treated successfully with nonsteroidal antiinflammatory drugs or analgesics and reassurance. One patient with a normal scan developed sarcoidosis; one, hypermobility syndrome; and one, a viral syndrome. Two patients had no diagnosis. Abnormal technetium Tc 99m medronate scans in patients with previously undiagnosed polyarthralgias suggested inflammatory arthropathy and influenced management decisions with favorable therapeutic outcomes.

Diphosphonate bone scans in patients with polyarthralgias

• Early detection of inflammatory arthropathy is notoriously difficult with standard radiographic techniques. We therefore assessed bone turnover with technetium Tc 99m medronate in 16 patients with persistent polyarthralglas who had no clinical synovitis, normal radiographs, and nondiagnostic results from laboratory evaluations. Abnormal scans were found in 11 of 16; five were unremarkable. Scan abnormality corresponded with symptomatic joints (11 of 11 patients). These 11 patients had normal test results for rheumatoid factor, antinuclear antibody, and HLA-B27. Patients with abnormal scans were treated with nonsteroidal antiinflammatory drugs or analgesics (11 of 11), hydroxychloroquine sulfate (four), or gold salts (one), with Improvement (nine of 11); patients with normal scans (five of five) were treated successfully with nonsteroidal antiinflammatory drugs or analgesics and reassurance. One patient with a normal scan developed sarcoidosis; one, hypermobility syndrome; and one, a viral syndrome. Two patients had no diagnosis. Abnormal technetium Tc 99m medronate scans In patients with previously undiagnosed polyarthralgias suggested inflammatory arthropathy and influenced management decisions with favorable therapeutic outcomes. (<i>Arch Intern Med</i>1988;148:1639-1642)

Treatment of the Patient With Rheumatoid Arthritis Refractory to Standard Therapy

SELECTED CASE AT THE age of 23 years, following a pregnancy, a woman developed severe fatigue, morning stiffness, and marked swelling and tenderness of multiple peripheral joints. On presentation to her physician, she was found to have serum rheumatoid factor in a high titer, an elevated erythrocyte sedimentation rate, and an elevated level of C-reactive protein. Roentgenographic studies revealed diffuse periarticular demineralization without bony erosions. A diagnosis of rheumatoid arthritis was made. During the next three years, the woman, in addition to undergoing physical therapy, was treated without significant or sustained improvement with several nonsteroidal anti-inflammatory drugs, hydroxychloroquine sulfate, gold salts, and penicillamine. In addition, treatment with low-dose prednisone was begun at a dosage of 5 to 10 mg orally per day. Moreover, she received many intra-articular injections of corticosteroids in many of her most troublesome joints to provide transient disease suppression in those joints. Progressive disease and disability were

Bullous Eruption in a Woman With Lupus Erythematosus

REPORT OF A CASE The patient, a 26-year-old woman, presented with a six-year history of systemic lupus erythematosus (SLE), which had been diagnosed in 1979. The diagnosis of SLE was made at the time of splenectomy for idiopathic thrombocytopenia purpura associated with antiplatelet antibodies. The patient also had leukopenia, anemia, a malar skin rash, arthralgias, cicatricial alopecia, photosensitivity, and positive serologic findings, including positive antinuclear antibody and anti-DNA tests. For the past five years, the patient's SLE was controlled with hydroxychloroquine sulfate (Plaquenil) and prednisone; azathioprine (Imuran) was added as a steroid sparing agent during the past three years. Her medical history was otherwise unremarkable except for minimal chronic active hepatitis seen on a liver biopsy performed at the time of splenectomy. In February 1985, the patient was doing well on a regimen of 20 mg of prednisone, 100 mg of azathioprine, and 300 mg of hydroxychloroquine sulfate per day.

Does hydroxychloroquine sulfate prevent clot formation in systemic lupus erythematosus?

Arthritis & RheumatismVolume 30, Issue 12 p. 1435-1436 LetterFree to Read Does hydroxychloroquine sulfate prevent clot formation in systemic lupus erythematosus? Daniel J. Wallace MD, Daniel J. Wallace MD Cedars-Sinai Medical Center Los Angeles, CASearch for more papers by this author Daniel J. Wallace MD, Daniel J. Wallace MD Cedars-Sinai Medical Center Los Angeles, CASearch for more papers by this author First published: December 1987 https://doi.org/10.1002/art.1780301219Citations: 100AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume30, Issue12December 1987Pages 1435-1436 RelatedInformation

Treatment of Discoid Skin Lesions With Azathioprine

To the Editor.— Tsokos et al 1 recently described a case of a young woman with systemic lupus erythematosus whose mild systemic disease was controlled with prednisone, hydroxychloroquine sulfate (Plaquenil), and triamcinolone acetonide (Aristocort) 0.1% cream, but whose discoid skin lesions progressed despite these therapies. The next step in her therapy was azathioprine sodium (Imuran) administered orally, which resulted in improvement of her skin lesions. We would like to emphasize that there are less toxic therapies that should be used to treat resistant skin lesions before resorting to cytotoxic agents. Several articles on antimalarial therapy 2,3 suggest that if hydroxychloroquine alone does not control extensive skin lesions, quinacrine hydrochloride (Atabrine) can be added synergistically without any increase in eye toxicity. Improvement has been seen in as many as 95% of patients in several series. 2 In our experience in the Bellevue Hospital Lupus Clinic, New York, nearly all patients who

Treatment of Intractable Rheumatoid Arthritis With Combined Cyclophosphamide, Azathioprine, and Hydroxychloroquine

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.

Successful Treatment of Generalized Discoid Skin Lesions With Azathioprine

A 20-year-old patient had systemic lupus erythematosus and extensive generalized discoid disease that failed to respond to conventional treatment with topical steroids and high doses of hydroxychloroquine sulfate (Plaquenil). The skin lesions responded dramatically to 100 mg of azathioprine sodium daily, flared when the drug treatment was discontinued, and again responded on reinstatement of the same dosage of azathioprine. The case report suggests that extensive discoid skin lesions can be successfully treated with oral azathioprine.

Hydroxychloroquine sulfate in rheumatoid arthritis: Long-term response rate and predictive parameters

Review of the records of 108 patients with rheumatoid arthritis who were treated with hydroxychloroquine sulfate for at least six months revealed that 63 percent responded: 12 percent achieved complete remission (no joint pain or tenderness, two or less joints with trace swelling); 14 percent showed a 75 percent response (75 percent or greater reduction in active joint count and 50 percent or greater reduction in morning stiffness); and 37 percent had between 30 percent (30 percent or greater reduction in active joint count and morning stiffness) and 75 percent response. Once response was obtained, flare-up of rheumatoid arthritis was uncommon. Only two of 108 patients developed retinopathy (subclinical); it resolved with drug discontinuation and did not cause visual deficits. Better grip strength and radiographs showing little articular damage at baseline might predict response to treatment with hydroxychloroquine. However, even though early disease may be more responsive, long-term rheumatoid arthritis does not preclude a good response to hydroxychloroquine.

Risk/benefit analysis of hydroxychloroquine sulfate treatment in rheumatoid arthritis

Controlled studies have their limitations in assessing the clinical effectiveness of drugs, particularly in patients requiring years of treatment. Retrospective analysis of long-term therapy can be useful and can be summarized easily by life-table analysis. Our first analysis revealed that side effects were more common in patients treated with gold than in those receiving hydroxychloroquine sulfate. Relapses in patients who were treated with gold occurred at a continuous rate over time, whereas in patients treated with hydroxychloroquine this rate leveled off after 20 months of treatment. Our second analysis revealed that the rate of drug discontinuation was lowest with hydroxychloroquine, followed—in order of discontinuation—by gold, D-penicillamine, and levamisole. In both studies, no definite retinopathy was seen in any patient. Since hydroxychloroquine is better tolerated and easier to use than D-penicillamine, gold, or levamisole, it is a reasonable choice for the first trial of a slow-acting antirheumatic drug.

Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment

The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. ∗ ∗ The manufacturer's recommendation is that Ophthalmologic examinations be made every three months during long-term therapy. Funduscopic examinations and visual field testing with a red object must be included. Although this protocol may detect abnormalities that are not drug related, no loss of vision has developed in patients so monitored.

Hydroxychloroquine Administration in Pregnancy

To the Editor.— In their excellent review article Tanenbaum and Tuffanelli 1 mention pregnancy as a contraindication to the use of chloroquine phosphate. I have been involved with this problem with one patient, a 23-year-old woman who was taking 200 mg/day of hydroxychloroquine sulfate during the first 16 weeks of pregnancy as a therapy for discoid lupus erythematosus. The pregnancy was allowed to proceed to full term. A healthy male infant was born. Follow-up examinations for two years have not shown any abnormality in the child's mental or physical development. Hart and Naunton 2 have described one family in which the mother had been taking chloroquine on and off, in excess of the recommended dose, for more than six years. Of a total of seven pregnancies, she had taken the drug during part or all of four of the pregnancies. These four pregnancies resulted in one miscarriage and three children

Generalized Ulcerative Sarcoidosis

Cutaneous involvement is present in approximately 25% of patients with sarcoidosis. A large variety of morphologic patterns has been well described; ulcerative lesions are rare. A 30-year-old black man had generalized cutaneous granulomas, many of which demonstrated superficial ulceration. The exudative quality of these lesions was probably secondary to recurrent bacterial infection. Use of oral antibiotics, prednisone, and hydroxychloroquine sulfate controlled his disease activity.

Heroic Treatment for Nonmalignant Disease

Severe progressive rheumatoid arthritis remains a therapeutic challenge. The usual approach has been described by Wilbur Blechman as resembling choices from a Cantonese restaurant menu—take one or more from column A and also from column B. Thus, the control of inflammation, or at least of the symptoms produced by inflammation, is made a responsibility of nonsteroidal antiinflammatory drugs and, in some cases, of corticosteroids. At the same time, inhibition of the progression of the disease generally requires addition of disease-modifying antirheumatic drugs, also known as remission-inducing drugs, such as gold salts, penicillamine, antimalarials, azathioprine, and a variety of experimental drugs and procedures borrowed from the treatment of other diseases. Gold compounds were first introduced because of a confusion between tuberculosis and rheumatoid arthritis; penicillamine began as an agent to remove copper from patients who had Wilson's disease; chloroquine and hydroxychloroquine sulfate were used to prevent or treat malaria, while azathioprine

Intractable Rheumatoid Arthritis

Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 ± 19 months (x̄±SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 ±1.2 to 2.7 ±3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use. (<i>JAMA</i>1982;248:1718-1723)

Hydroa Vacciniforme

Hydroa vacciniforme is a rare, chronic photodermatosis with onset in childhood. Multiple exposures to UV-A reproduced the symptoms and the vesicular and scarring lesions typical of the sun-induced disease in our patient. Treatment with hydroxychloroquine sulfate, but not indomethacin, reduced the photosensitivity both to sunlight and to artificial UV-A light. Serum complement levels were low while the disease was active and returned to normal after treatment of the patient with hydroxychloroquine.

Hydroxychloroquine. Seven-year experience.

Ninety-nine patients were treated with hydroxychloroquine sulfate for connective tissue diseases during a seven year period. All patients received the medication for at least one year and most were treated with a daily dosage of 400 mg. Four patients experienced toxic effects, but no patient sustained permanent loss of visual acuity. Toxicity did not seem to represent a cumulative dosage effect. Funduscopic and visual field examinations at six-month intervals are sufficient to detect the occasional adverse reactions and prevent serious retinal toxic effects when a maximum daily dosage of 400 mg is maintained.

Hydroxychloroquine Treatment of Porphyria Cutanea Tarda

Six patients with skin changes and urinary porphyrin excretion patterns characteristic for porphyria cutanea tarda were treated with hydroxychloroquine sulfate therapy. During treatment periods ranging from five to 13 months, cutaneous symptoms disappeared and urinary porphyrin excretion abnormalities were completely or almost completely reversed. In three subjects, hydroxychloroquine therapy was accompanied by changes in the urinary excretion of iron. The first four patients, followed up for nine to 24 months after treatment, all had relapse, and substantial porphyrinuria developed once more; cutaneous symptoms recurred in two of these. Three of the four patients were re-treated, and their conditions again improved or went into remission with hydroxychloroquine therapy. In two patients, treatment responses were slower than those initially seen, despite the use of higher drug doses; in the third patient, the response to re-treatment was more rapid than that seen during the first treatment course.

Antimalarial Agents

Chloroquine phosphate and hydroxychloroquine sulfate are substituted 4-amino quinoline compounds that differ only by a hydroxy group. Quinacrine hydrochloride also has the 4-amino quinoline radical but has, in addition, a benzene ring; it is classified as an acridine compound. The 4-amino quinoline radical is present in all antimalarial compounds shown to be effective in the treatment of lupus erythematosus (LE) (Figure).¹ <h3>HISTORY</h3> Quinacrine was introduced for malaria therapy in 1930. Its superiority over quinine was established during World War II, when it became the official drug for the treatment of malaria. The toxicity of quinacrine and its inability either to cure malaria or to act as an effective prophylactic, however, spurred continued research for better drugs. A large series of 4-amino quinolines were investigated. Of these, chloroquine proved to be the most promising and was released for field trial.²By the end of World War II, it had