Edmund L. Dubois

Antimalarials in the management of discoid and systemic lupus erythematosus

A NTIMALARIALS have been used in the treatment of discoid lupus erythematosus (DLE) since 1894, when Payne’ tried quinine. He considered the disease to be a circulatory disturbance and noted marked pallor in patients given large doses of quinine; however, it was not until Page’s report’ in 1951 that these drugs were widely employed in the English-speaking countries. Martenstein” in 1928 treated 28 patients with discoid and subacute systemic lupus erythematosus (SLE) with pamaquine (Plasmochin), which is similar to quinine in that both are substituted 8-aminoquinolines. Good results were obtained in 22 patients. He noted that active and acutely inflamed lesions responded more rapidly than hyperkeratotic indolent lesions. Although pamaquine was widely used by European physicians for the treatment of LE, there were no other formal reports of its effectiveness. Davidson and Birt’ in 1938 reported excellent results in 19 of 29 patients treated with quinine bisulfate. In 1941, Prokoptchouk”,” successfully treated 35 patients with DLE by giving 100 mg of Atabrine (quinacrine, mepacrine) three times daily for IO days, alternating with IO-day rest periods. Sorinson’ treated 70 patients by this method, with the majority requiring five or more courses of Atabrine to obtain benefit. These earlier findings, however, were not generally known in the English speaking countries until Page’ independently discovered the remarkable effect of Atabrine when he purposely administered it to a patient with longstanding discoid lesions after quinine and other forms of therapy had failed. He reported a series of 18 lupus patients, including two with DLE and “rheumatoid arthritis,” who noted improvement in their arthritis as well as the skin lesions, and another with typical SLE who responded favorably. There was improvement in the cutaneous lesions in 17 of the 18 cases. These findings were quickly confirmed in this country by O’Leary et al.,x who stated, however, that systemic involvement was a contraindication to Atabrine therapy. Numerous other investigators confirmed the beneficial effects of Atabrine for DLE.!“’ Subsequently it was shown clearly that other antimalarials were also quite effective. Goldman et al.” reported that chloroquine was helpful in 21 patients, including three with subacute disseminated disease. Pillsbury and Jacobson’” reported excellent results in 15 of 16 patients taking chloroquine, but pointed out that six of them relapsed 448 wk after stopping treatment. Hydroxychloroquine (Plaquenil) subsequently was investigated by many workers and found to be as effective as chloroquine, with fewer side effects. ‘*-” Many patients who were unable to tolerate chloroquine could take hydroxychloroquine, and vice versa. Amodiaquin (Camoquin) has also been used with good results.‘x-“‘l To evaluate the effectiveness of medication for DLE, it is essential to know the incidence of spontaneous remissions. In our own studies, 10% of patients had a history of spontaneous improvement. ” In the series of Herrman et al.,“z 14% of patients healed spontaneously, compared with 85% or better improvement in antimalarial-treated cases.2”+‘” The writer was one of the first to study consistently the effect of antimalarials in the management of SLE. Initially, doses as large as 2000 mg/day of Atabrine for 60 days were employed. The clinical results varied with the severity of the disease. A series of 37 patients were reported in 1954.” In general, the less active the systemic spread and the greater degree of cutaneous involvement, the better the results. Improvement occurred in systemic complaints even in patients without cutaneous involvement. It was noted that frequently the dosage of corticosteroid could be reduced and

Lupus nephritis: Experience with 230 patients in a private practice from 1950 to 1980

Nephritis developed in 230 of 609 private patients with systemic lupus erythematosus (SLE) (38 percent) followed up from 1950 to 1980. Eighty-seven percent of patients with nephritis were female; 71 percent were Caucasian. They were observed a mean of 10 years. Five- and 10-year survival rates were 80 percent and 65 percent, with improvement to 86 percent and 76 percent in the last decade. Normalization of urinary sediment and protein levels, blood pressure and serum albumin levels correlated with improved survival and tended to occur during the first year. Life-threatening complications of SLE were more common after the onset of nephritis but decreased as renal function worsened. Infection was the most frequent cause of death in the last decade. Forty-four patients received nitrogen mustard; 55 percent of the courses were followed by significant improvement in renal function and reduced steroid dosage. Control of the disease was associated with improved long-term survival of patients with SLE.

Long-Term Course of Chloroquine Retinopathy after Cessation of Medication

Seven patients with chloroquine retinopathy were examined ten years after their therapy with chloroquine or hydroxychloroquine, or both, had been discontinued and an additional five patients with chloroquine retinopathy were similarly examined from two to eight years after their therapy had been discontinued. Visual acuity, visual fields, and ophthalmoscopic examinations were compared to those performed at the time therapy was discontinued. These long-term observations confirmed the previously published observations based on short-term studies that chloroquine retinopathy tends to remain stable after therapy is discontinued, although a few patients in the early stages of retinopathy may show regression and occasionally a patient with a more advanced stage of the disease may show progression.

Failure of procainamide to induce a systemic lupus erythematosus-like disease in animals☆

Abstract Procainamide induces a systemic lupus erythematosus-like (SLE) syndrome in humans. Although 77% of cardiac patients receiving the drug for 6 wk or more developed LE cells and antinuclear antibodies without clinical signs of SLE, we found no evidence that it produced similar abnormalities in animals. Seven dogs received doses as high as 588 mg/kg/day for periods up to 34 wk. Hybrid NZB NZW mice which spontaneously develop an SLE-like syndrome were treated with doses as high as 2 g/kg/mouse/day in order to determine whether the drug would aggravate the disease. There was no difference in the course or life span of 59 treated hybrids from that of the 31 littermate controls. Pilot studies were done giving large amounts of procainamide to 4 white rats, 4 guinea pigs, 1 hamster, and 1 minipig for as long as 39 wk with similar negative results. To date, drug-induced lupus has not been clearly duplicated in any animal. The failure to provoke changes in other species similar to those induced in humans suggests that there may be significant differences in etiologic factors between the animal model and human SLE. Caution should be used in implying that data obtained from lupuslike animal diseases are pertinent to humans.

Lupus Erythematosus, Lupoid Syndromes and Their Relation to Collagen Diseases, Part 1

Lupus erythematosus, a variant of “rheumatoid arthritis,” is a common disease which has a wide clinical spectrum ranging from the mild form with or without minor systemic manifestations (discoid lupus) to the malignant disseminated or systemic type. Evidence for a unitary theory of these forms is presented, as well as a discussion of their relation to rheumatoid arthritis. The tendency for occurrence of transitional forms between all these disorders, with progression from one to another, is emphasized. Newer forms of therapy have produced dramatic benefit in discoid lupus and have prolonged life appreciably in the systemic type.

Total exchangeable potassium in systemic lupus erythematosus with reference to "triamcinolone myopathy".

Summary Total exchangeable potassium, using K42, was determined in a group of female control subjects and 2 groups of patients with systemic lupus erythematosus. One of these groups was receiving adrenal cortical steroids including triamcinolone, the other salicylates and antimalarials only. Serial determinations were also done on one patient receiving long term steroid therapy. No significant differences in total exchangeable potassium values could be demonstrated among the 3 groups, and steroid therapy, including triamcinolone, did not appear to have an effect on total exchangeable potassium. The authors are indebted to Juanita Lestina and Marva Jenkins for their technical assistance.

Raynaud Phenomenon in Pregnancy-Reply

In Reply.— Regarding the letter of Dr Cook concerning the lethal effect of renal scleroderma on mother and fetus, it is true that patients in whom preeclampsia and eclampsia associated with the acute onset of renal scleroderma develop have a poor prognosis. Unfortunately, in the presence of normal renal function and blood pressure, the subsequent appearance of renal scleroderma cannot be predicted. Fortunately, however, the incidence of pregnancy in scleroderma is low, probably due to the effects of the disease on fertility. Even without pregnancy, progressive systemic sclerosis may undergo an acute exacerbation with sudden appearance of malignant hypertension secondary to renal involvement. Karlen and Cook ( Obstet Gynecol 44:349, 1974) report on such a case and summarize the literature on 17 other cases, in four of which there were maternal deaths caused by renal involvement, without clinical evidence prior to or during early pregnancy. A less biased view is obtained by