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Systemic Lupus Erythematosus: Important considerations in the adolescent
JOURNALOF ADOLESCENTHEALTHCARE2:273-278,1982
Systemic Lupus Erythematosus: Important Considerations in the Adolescent D A V I D J. N A S H E L , M.D. A N D CHERYL C. ULMER, M.S.
Systemic Lupus Erythematosus (SLE) may be particularly devastating to the adolescent female because of the marked changes in appearance w h i c h may result from the disease and by its treatment. Attention is drawn to the potential of the patient manipulating her medications in response to these changes. Other special considerations include the unique side-effects of corticosteroid and antimalarial drugs, the need to distinguish psychological reactions to SLE from true organic involvement and an added risk for a flare of disease activity in the sexually active patient. A case of a teenage female with SLE is used to illustrate some of the management problems which may be encountered.
face and extremities and diffuse thinning of the hair. In addition, therapy with corticosteroids and antimalarial agents may contribute to significant changes in the patient's personali ~ . . . . . . . nce These aspects of the diseas,~ L t y anu al_,p.¢.al,*~" ,- ,iLay De anxiety pw" voking, particularly for young females trying to accomplish the normative psychosocial tasks of adolescence. The case which follows, illustrates some of the difficulties the physician may encounter in caring for the adolescent with SLE.
KEYWORDS: Systemic lupus erythematosus Adolescence Drug compliance "
The patient, a white female, had been in her usual state of good health when at 14 years of age she developed oral ulcerations, frontal hair loss, and an erythematous eruption over her rnalar regions. Initially, the rash responded to oral tetracycline and topical corticosteroid cream. Shortly thereafter, the patient began having severe pain involvin~ her vroximal interphalangeal (PIP) and met acarpopnalangea % , i -1 (MCP) joints, began tiring easily, and had fevers to 104°F. She was admitted to Georgetown University Hospital where examination revealed a weight of 106 lbs., height 60 in., temperature 99.4OF., and blood pressure 110/62. There were tender vasculitic lesions about the nail beds, in the pulp of the finger tips, and there was an erythematous rash n~r~r the ........ elbows and fac e • She had obvlo " us frontal alopecia. Joint examination showed swelling of the wrists, knees, and the second through fifth PIP joints bilaterally and second through fourth MCP joints bilaterally• Prior to admission the patient was having regular menstrual periods. Her stage of secondary sexual development was' Tanner IV. Laboratory examination revealed a hematocrit of 30%, noranal RBC morphology, WBC 3600 cells/
Case Report
Systemic lupus erythematosus (SLE) is a connective tissue disorder characterized by multiple organ involvement and the presence of a variety of autoantibodies• This disease, primarily affecting females, occurs in all age groups but the peak age of onset of the first s y m p t o m is between 15 and 25 years of age (1). These patients may pose special problems to the managing physician. A m o n g the frequent manifestations of SLE activity are skin lesions involving the From the Rheumatology Section, Department of Medicine, Veterans Administration Medical Center, and Georgetown University School of Medicine, Washington, D.C.; and the Office of the Assistant Secretary for Planning and Evaluation~Health, Department of Health and Human Services, Washington, D.C. Send reprint request to: David J. Nashel, M.D., Chief, Rheumatology Section, Room 3A161, V.A. Medical Center, 50 Irving Street, N.W., Washington, D.C. 20422. Manuscript accepted October 16,1981.
© Societyfor AdolescentMedicine,1982 Publishedby ElsevierSciencePublishingCo., Inc.,52 VanderbiltAve., New York,NY 1 0 0 1 7
273 0197-0070/811040273-06502.75
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m m 3, normal urinalysis, Westergren sedimentation rate of 95 mm/hr, positive lupus erythematosus (LE) cell preparation, strongly positive fluorescent antinuclear antibody test in a diffuse pattern with a titer of 1:320, total hemolytic complement of 58 (normal 100-200), and positive anti-DNA antibodies. A diagnosis of SLE was made. Treatment and its Side-effects
Since the patient was toxic in appearance and because she had widespread vasculitic lesions, 45 mg of prednisone in divided doses was started. An ophthalmologic examination was normal and hydroxychloroquine 200 mg a day was added to the treatment regimen. The major side-effects of these medications were discussed with the patient and her parents. On therapy she showed a marked decrease in joint pain and within 2 weeks there was resolution of most of her skin lesions. Prior to discharge from the hospital a special emphasis was placed on educating the patient and her family about SLE and it's particular treatment requirements. They were informed that there are many variations in SLE disease expression and intensity and for this reason some patients require more careful monitoring and more medication than others. After 3 weeks of therapy the patient had become noticeably cushingoid. Her hematocrit had risen to 35%, Westergren sedimentation rate was 20 mm/hr, and total hemolytic complement had increased to 81. The prednisone dose was reduced by an average of 5 mg each week over the next 2 months. Because the patient had intermittent arthralgias and arthritis, recurrent mucosal ulcerations and a few periungual vasculitic lesions, she was maintained on 20 mg of prednisone a day. Serum total hemolytic complement levels remained in the low normal range, immunoglobulin G levels were mildly elevated, and antinuclear antibody test was positive at a titer of 1:180. Over the next several years the patient's disease was characterized by moderate exacerbations of arthritis, fever, skin rash, and vasculitic lesion on the fingers and elbows. Her prednisone dose ranged between 10 and 20 mg a day, depending on disease activity, and she was maintained on hydroxychloroquine 200 mg a day. The patient was seen at 2-4 week intervals. On each visit, in addition to routine CBC and urinalysis, blood was drawn for Westergren sedimentation rate and serum complement determination. Immunoglobulin G levels, titer of antinuclear antibodies, and 24-hr urine protein
JOURNALOF ADOLESCENTHEALTHCAREVol. 2, No. 4
quantitation was performed at 3-4 month intervals. On many occasions the patient expressed concern about the side-effects of her medications. She was particularly worried about her cushingoid appearance, an acneiform eruption over the face and arms, and obvious striae over the buttocks, thighs, and lower legs. She was also aware of a slight yellowish tinge to her skin. It was explained to the patient and her parents that these troublesome side-effects would improve significantly when, disease activity permitting, her drug dosages were further reduced. The patient found this counsel to be comforting, and was better able to cope with her disease. Psychological Reactions to the Illness
Following discharge from her initial hospitalization, the patient became increasingly depressed. She indicated particular unhappiness about having to see a doctor on a regular basis and the prospect of having to take drugs indefinitely. The patient was argumentative and short-tempered with friends and relatives and became increasingly disinterested in her school work. When she refused psychiatric help, an aunt with w h o m the patient was particularly close was asked to assist in her emotional support. Her intervention produced a dramatic improvement in the patient's frame of mind. At age 16 years, a family member disclosed that the patient had become increasingly irritable with marked mood swings. A diagnosis of central nervous system lupus was entertained. A careful physical examination failed to reveal neurologic deficits. The patient's cognitive function was intact, and laboratory parameters of disease activity, including Westergren sedimentation rate, serum complement and immunoglobulin G level, were normal. It was felt that the patient's emotional lability represented a functional disorder. She gradually improved without change in her prednisone dose of 10 mg once a day. Compliance
At age 17 years, on a routine visit, the patient for the first time admitted that she was not taking the prednisone as prescribed. She was increasingly concerned about her facial appearance and increased weight. Because of a planned trip to Europe, she was anxious to be more attractive. In spite of admonitions to avoid sun exposure, especially during midday, the patient spent long hours in the sun while in Europe. She noted that following such ex-
June 1982
posure there was a marked increase in rash over the face and she was more easily fatigued by activity. On her own initiative she increased her prednisone dose from 10 to 20 mg a day, and the rash and fatigue improved. The importance of strict drug compliance was continuously stressed to the patient, yet on several subsequent visits she admitted to manipulating her medications. Sexual Concerns
Shortly after her 18th birthday, the patient broached the subject of marriage and the possibility of having children. She was concerned about how her boyfriend might react if he knew fully about her illness. She admitted having sexual relations without contraceptive protection. The patient was informed that birth control pills might exacerbate SLE and that pregnancy might be dangerous unless the disease was under optimal control. She was referred to a gynecologist for contraceptive advice and received instructions on the use of a diaphragm. It was felt that an intrauterine device posed an additional risk as a potential source of infection. Course of the Disease
Five years after her initial hospitalization the patient presented with pleuritic chest pain and was found to have a loud pericardial friction rub. For the first time her urinalysis was abnormal with protein of 1.2 g/24 hr. Urinalysis 2 months before had been normal. Westergren sedimentation rate was now 91 and serum complement level was 70. A renal biopsy disclosed diffuse proliferative glomerulonephritis. In spite of the patient's reservations, her corticosteroid dosage was increased to 30 mg of prednisone a day in divided doses. The pericarditis rapidly resolved and the proteinuria gradually subsided over the next two months. Since that time, the patient's disease had been successfully controlled on 10 mg of prednisone a day in a single dose, and 200 mg of hydroxychloroquine. The patient now has been dealing with her disease with greater equanimity perhaps a reflection of her psychosocial maturation. Her relationship with her parents and siblings has improved significantly.
Discussion The previous case illustrates many problems that may confront the physician treating an adolescent with SLE. The emotional strain of this chronic dis-
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ease is intensified by the potentially disfiguring features of the disease and its treatment. This occurs at a time w h e n body image is fragile and the need for acceptance by peers is peaking. The following physical and emotional aspects of the illness in the adolescent deserve special consideration. Among the physical manifestations of SLE, often the most disturbing to the adolescent are dermatitis, alopecia and vasculitic lesions. The most easily recognized skin lesion is the butterfly eruption. Although it is often photosensitive, it usually heals without scarring. If erythema persists, it can often .be masked by the use of special covering makeup (such as Cover Mark). Discoid skin lesions, which frequently involve the face and scalp, are more dif: ficult to manage. This rash is often scaly and it heals with atrophic areas with varying pigmentation. These scarring lesions are distressing to the adolescent. Fortunately, there is often improvement with local corticosteroid therapy. For many patients exposure to the sun not only exacerbates the skin lesions but it may lead to a generalized increase in disease activity. It is therefore best for these patients to avoid direct sun light. When this is not possible, the use of sun screen agents containing para-aminobenzoic acid (PABA) is advisable (2). The physician often has difficulty dissuading the adolescent patient from going to the beach or sitting by the pool during the summer. A compromise is to have the patient swim at the beginning or end of the day w h e n the sun's rays are less direct. Diffuse hair loss is common in active SLE. Usually the loss of hair is most prominent in the frontal areas. If the alopecia is severe, the patient can avoid embarrassment by using a wig. Vasculitic skin lesions involving the elbows and fingers are also common manifestations o f SLE. In addition to being painful, these lesions may be unsightly. Along with periungual erythema and nail fold infarcts, nail lesions and onycholysis are common (3). The patient can be reassured that hair often grows back w h e n the disease activity lessens, and thatowith proper therapy the skin lesions can be controlled. The adolescent SLE patient soon learns that their chronic disease has a propensity for exacerbations and remissions. Because of this variability in disease activity, assymptomatic patients must be followed regularly with blood and urine studies performed at one to three month intervals. It is not unusual for patients with active r6nal or pleuropulmonary disease to require follow-up at weekly intervals. The adolescent may feel that this significantly interferes
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with some of their school and social activities. More importantly, there is the realization that they are not "'normal" and that their illness sets them apart from their peers. Hall and his associates found that patients who sever social relationships tend to have exacerbations of disease twice as frequently as those who remain socially active (4). Thus it seems important to ensure that the teenager does not become isolated from his or her peers. Klippel and Zvaifler state that, "depression often coincides with the onset of disease or with the institution of adrenal corticosteroid therapy for the systemic features of SLE" (5). The patient described earlier experienced a variety of emotional responses to her disease including periods of depression and episodes of anxiety. As with any chronic illness, the patient may exhibit a wide range of psychological reactions. The intensity of these responses, as Blumen field note s, "will depend on the degree of illness, particular symptoms and of course the psychological make-up of the patients" (6). While depression is not unexpected in a prolonged illness, this disturbance of mental function is particularly common in lupus patients. For the adolescent this is understandable. The disease and the medications used to treat it not only cause marked changes in appearance, but also cause the patient to question whether they will be able to pursue their life goals of work, marriage, and childbearing. Their ultimate fear is that of premature death. Educational counseling by the physician on the course and nature of the disease is important to arrest unfounded fantasies, Efforts must be particularly directed at dispelling the popular myth that the disease is invariably fatal. Because of the frequency of contact and the opportunity to develop personal rapport, the primary care physician is the most important source of psychiatric support. More structured psychiatric intervention is advisable if the patient develops severe depression, psychotic episodes, or has suicidal tendencies. It is particularly important for the physician to distinguish these psychological reactions from true central nervous system involvement. SLE is somewhat unique in that involvement of the central nervous system is a frequent part of the disease process. It is usually characterized by disturbances in mental function (5). Organic psychiatric syndromes have been reported in as many as 42% of patients with SLE (7). There is evidence that both vascular and immune mechanisms are involved in its pathogenesis (8). As pointed out by Guze (9), there is a remarkable variability in the clinical picture of SLE
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induced psychiatric illness. The organic syndromes reflecting cerebritis or ence~0halitis are often characterized by impaired cognitive function, i.e., changes in orientation, memory, or perception (5). This is the most serious form of neurologic disease and requires high-dose corticosteroid therapy. Patients with nonorganic syndromes usually have normal cognitive function. The most common functional disorder is depression, often characterized by emotional lability, insomnia, and spontaneous crying (4). These individuals usually respond to reassurance and family support but at times may also require psychotherapy. Since SLE patients often require significant doses of corticosteroids for protracted periods of time, the physician must be familiar with the common sideeffects: facial mooning, weight gain, edema, hypertrichosis, ecchymotic lesions, acne, and striae. These features are understandably distressing to the adolescent w h o is sensitive to changes in body image. In some instances, high doses of corticosteroids result in the cessation of menstrual periods. In addition, corticosteroid therapy itself may be complicated by serious psychological disturbances (10). This is particularly true with the high dosages (11). While there is no way of predicting which patients will have a psychological reaction to corticosteroids, those individuals with known psychological problems experience more frequent and more serious disturbances (12). Another potential consequence of corticosteroid therapy is the development of significant osteoporosis. This takes on added significance when one considers the metabolic needs of the growing adolescent. Recently it has been shown that there are reduced serum levels of 1,25-(OH)2 vitamin D3 in prednisone-treated adolescents with SLE (13). As a consequence, these patients may require supplemental vitamin D. The physician should encourage the patient to be physically active since this may retard osteoporosis and enhance the feeling of wellbeing. SLE patients with arthritis or skin rash can usually be satisfactorally managed with antimalarial and anti-inflammatory drugs. But corticosteroids may be required on an intermittent basis and should be used in the lowest possible dose sufficient to suppress the disease. Westergren sedimentation rate, i m m u n o globulin G and serum complement levels are the most useful laboratory parameters for assessing disease activity. Reduction in serum complement may antedate exacerbation of disease by months (14). Physical examination and serologic measurements
June 1982
are both important in determining corticosteroid dose. However, isolated laboratory, abnormalities are not a justification for changing amounts of medication. At times an alternate day schedule of corticosteroid administration is effective in controlling SLE and may ameliorate the manifestations of Cushing's syndrome (15). Yet, while most of the side-effects of corticosteroids can be avoided with alternate day doses, this regimen is often ineffective in controlling SLE, particularly w h e n there is renal, cardiac, or central nervous system involvement. Patients taking prednisone on a daily basis can expect to lose the moon facies, once it has developed, only after the dose is reduced to between 5 and 10 mg a day, The patient requires repeated reassurance from the physician that the changes associated with corticosteroid therapy will regress w h e n the dosage is eventually lowered. Another drug commonly used in the management of skin rash and the arthritis associated with SLE is the antimalarial agent hydroxychloroquine. It is generally given in a dose of between 200 and 400 mg a day. The major side-effect of this drug is retinal toxicity. However, with regular ophthalmologic examinations and visual field testing repeated at 6-month intervals, hydroxychloroquine may be safely used (16). The physician must be alert to the fact that this drug may on occasion cause irritability, emotional changes, nightmares, and even psychosis (17). In addition it may induce alopecia, yellowish pigmentation of the skin, bleaching of the hair, and a variety of skin eruptions which may be confused with the dermatologic manifestation of SLE. However, these toxic reactions are rare if the dose is kept at 400 mg or less a day. As with corticosteroids, the side-effects of this medication generally regress with a lower dose, i.e., 200 mg every other day. Of particular concern to young w o m e n with SLE is the affect the disease may have on their ability to bear children. They often w o n d e r if the child will inherit the disease. The patient should be reassured that having SLE does not preclude child bearing, but that pregnancy does entail some increased risks for both mother and child particularly w h e n the disease is active. The association of certain B-cell alloantigens with SLE suggests that genetics does play a role in the etiology of this disease (18). Therefore, a child of an SLE mother may be at additional risk to develop the disorder, but this rarely occurs. If the adolescent patient with SLE is sexually active, she should be made aware of the potential for the pregnancy or an abortion to cause a serious flare
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in the disease. In addition, a young women with a chronic disease may find child care unduly stressful, In general, it is best to defer pregnancy until th.e disease is under good control (19). The question of contraception is a delicate topic for discussion between physician and adolescent. Since birth control pills may cause a lupus-like diathesis or a flare in preexisting SLE disease, it is best to avoid these agents and to recommend another form of contraception. At times it may be difficult for the adolescent to decide which is more disturbing, the lesions as.sociated with SLE or the side-effects of the medications used. Not infrequently the patient will secretly reduce the dose of corticosteroid to avoid being cushingoid. The physician must be alert to this and should emphasize to the patient •the serious consequences that may ensue from inadequately controlled disease. As James Masterson writes, adolescence !s "a stage in individual growth and development which has been notorious throughout the centuries as One of great emotional upset with wide fluctuations in behavior" (20). Add to this milieu a disfiguring disease, one can readily understand the potential for psychological disturbances. The physician plays a primary role in helping the patient cope with the disease. Adolescents require constant support in interpreting how the disease is affecting them as individuals, rather than textbook discussions of the illness. It is essential that the family be involv.ed early in this process. The parents often have a difficult task. On one hand they must not allow the child to develop undue dependence and should encourage her to live a productive life without indulgence in self pity. On the other hand, parents have to assure that medications are taken correctly and that proper limitations of stressful activities are observed. Patients may t ~ to assert their independence by manipulating their medications or by attempting to function on the same level as their peers. However, with reassurance and emotional support appropriate for the patient's age, the adolescent with SLE°can usually withstand the vicissitudes of the illness and successfully negotiate t h e psychological and social developmental tasks of adolescence.
References 1. Rothfield N: Clinical features of systemic lupus erythematosus, in KellyWN, Harris ED, Ruddy S, et al. (eds):Textbook of Rheumatology. Philadelphia, W.B. Saunders, 1981, pp. 1106,1132.
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2. Furey NL, Esterly NB: Lupus erythematosus. Major Prob Clin Pediatr 19:367-403,1978. 3. Urowitz MB, Gladman DD, Chalmers A, et al.: Nail lesions in systemic lupus erythematosus. J Rheumatol 5:441-447, 1978. 4. Hall RCW, Stickney SK, Gardner ER: Psychiatric symptoms in patients with Systemic lupus erythematosus. Psychosomatics 22:15-24,1981. 5. Klippel JH, Zviafler NJ: Neuropsychiatric abnormalities in systemic lupus erythematosus. Clin Rheum Dis 1:621-638, 1975. 6. Blumenfield M: Psychological aspects of systemic lupus erythematosus. Primary Care 5:159-171,1978. 7. Estes D, Christian CL: The natural history of systemic lupus erythematosus by prospective analysis. Medicine 50:85-95, 1971. 8. Bresnihan B, Hohmeister R, Cutting ], et al.: The neuropsychiatric disorder in systemic lupus erythematosus: Evidence for both vascular and immune mechanisms. Ann Rheum Dis 38:301-306,1979. 9. Guze SB: The occurrence of psychiatric illness in systemic lupus erythematosus. Am J Psychiatry 123:1562-1570,1967. 10. Carpenter WT Jr., Bunney WE Jr.: Effects of cortisol in man. Seminars Psychiatry 3:421-434,1971. 11. The Boston Collaborative Drug Surveillance Program: Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 13:694-698,1972.
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12. Williams GH, Dluhy RG, Thorn GW: Diseases of the adrenal cortex, in Isselbacher KJ, Adams RD, Braunwald E, et al. (eds): Harrison's principals of internal medicine. New York, McGraw HiII, 1980, pp. 17!1-1736. 13. O'Regan S, Chesney RW, Hamstra A, et al.: Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand 68:109-111,1979. 14. Singsen BH, Bernstein BH, King KK: Systemic lupus erythematosus: C~rrelations between changes in disease activity and serum complement levels. J Pediatr 89:358-365,1976. 15. Axelrod L: Glucocorticoid therapy. Medicine 55:39-65,1976. 16. Rynes RI, Krohel G, Falbo A, et al.: Ophthalmologic safety of long-term hydroxychloroquine treatment. Arthr Rheum 22:832-836,1979. " 17. Dubois EL: Systemic lupus erythematosus: Recent advances in its diagnosis and treatment. Ann Intern Med 45:163-184, 1956. 18. Reinertsen JL, Klippel JH, John AH, et al.: B-lymphocyte alloantigens associated with systemic lupus erythematosus. N Engl J Med 299:515-518,1978. 19. Steinberg AD: Management of systemic lupus erythematosus, in Kelly WN, Harris ED, Ruddy S, et al. (eds): Textbook of Rheumatology. Philadelphia, W.B. Saunders, 1981, pp. 1133-1150. 20. Masterson JF Jr.: The psychiatric dilemma of adolescence. Boston, Little, Brown Co., 1967.
Systemic Lupus Erythematosus: Important Considerations in the Adolescent D A V I D J. N A S H E L , M.D. A N D CHERYL C. ULMER, M.S.
Systemic Lupus Erythematosus (SLE) may be particularly devastating to the adolescent female because of the marked changes in appearance w h i c h may result from the disease and by its treatment. Attention is drawn to the potential of the patient manipulating her medications in response to these changes. Other special considerations include the unique side-effects of corticosteroid and antimalarial drugs, the need to distinguish psychological reactions to SLE from true organic involvement and an added risk for a flare of disease activity in the sexually active patient. A case of a teenage female with SLE is used to illustrate some of the management problems which may be encountered.
face and extremities and diffuse thinning of the hair. In addition, therapy with corticosteroids and antimalarial agents may contribute to significant changes in the patient's personali ~ . . . . . . . nce These aspects of the diseas,~ L t y anu al_,p.¢.al,*~" ,- ,iLay De anxiety pw" voking, particularly for young females trying to accomplish the normative psychosocial tasks of adolescence. The case which follows, illustrates some of the difficulties the physician may encounter in caring for the adolescent with SLE.
KEYWORDS: Systemic lupus erythematosus Adolescence Drug compliance "
The patient, a white female, had been in her usual state of good health when at 14 years of age she developed oral ulcerations, frontal hair loss, and an erythematous eruption over her rnalar regions. Initially, the rash responded to oral tetracycline and topical corticosteroid cream. Shortly thereafter, the patient began having severe pain involvin~ her vroximal interphalangeal (PIP) and met acarpopnalangea % , i -1 (MCP) joints, began tiring easily, and had fevers to 104°F. She was admitted to Georgetown University Hospital where examination revealed a weight of 106 lbs., height 60 in., temperature 99.4OF., and blood pressure 110/62. There were tender vasculitic lesions about the nail beds, in the pulp of the finger tips, and there was an erythematous rash n~r~r the ........ elbows and fac e • She had obvlo " us frontal alopecia. Joint examination showed swelling of the wrists, knees, and the second through fifth PIP joints bilaterally and second through fourth MCP joints bilaterally• Prior to admission the patient was having regular menstrual periods. Her stage of secondary sexual development was' Tanner IV. Laboratory examination revealed a hematocrit of 30%, noranal RBC morphology, WBC 3600 cells/
Case Report
Systemic lupus erythematosus (SLE) is a connective tissue disorder characterized by multiple organ involvement and the presence of a variety of autoantibodies• This disease, primarily affecting females, occurs in all age groups but the peak age of onset of the first s y m p t o m is between 15 and 25 years of age (1). These patients may pose special problems to the managing physician. A m o n g the frequent manifestations of SLE activity are skin lesions involving the From the Rheumatology Section, Department of Medicine, Veterans Administration Medical Center, and Georgetown University School of Medicine, Washington, D.C.; and the Office of the Assistant Secretary for Planning and Evaluation~Health, Department of Health and Human Services, Washington, D.C. Send reprint request to: David J. Nashel, M.D., Chief, Rheumatology Section, Room 3A161, V.A. Medical Center, 50 Irving Street, N.W., Washington, D.C. 20422. Manuscript accepted October 16,1981.
© Societyfor AdolescentMedicine,1982 Publishedby ElsevierSciencePublishingCo., Inc.,52 VanderbiltAve., New York,NY 1 0 0 1 7
273 0197-0070/811040273-06502.75
274
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m m 3, normal urinalysis, Westergren sedimentation rate of 95 mm/hr, positive lupus erythematosus (LE) cell preparation, strongly positive fluorescent antinuclear antibody test in a diffuse pattern with a titer of 1:320, total hemolytic complement of 58 (normal 100-200), and positive anti-DNA antibodies. A diagnosis of SLE was made. Treatment and its Side-effects
Since the patient was toxic in appearance and because she had widespread vasculitic lesions, 45 mg of prednisone in divided doses was started. An ophthalmologic examination was normal and hydroxychloroquine 200 mg a day was added to the treatment regimen. The major side-effects of these medications were discussed with the patient and her parents. On therapy she showed a marked decrease in joint pain and within 2 weeks there was resolution of most of her skin lesions. Prior to discharge from the hospital a special emphasis was placed on educating the patient and her family about SLE and it's particular treatment requirements. They were informed that there are many variations in SLE disease expression and intensity and for this reason some patients require more careful monitoring and more medication than others. After 3 weeks of therapy the patient had become noticeably cushingoid. Her hematocrit had risen to 35%, Westergren sedimentation rate was 20 mm/hr, and total hemolytic complement had increased to 81. The prednisone dose was reduced by an average of 5 mg each week over the next 2 months. Because the patient had intermittent arthralgias and arthritis, recurrent mucosal ulcerations and a few periungual vasculitic lesions, she was maintained on 20 mg of prednisone a day. Serum total hemolytic complement levels remained in the low normal range, immunoglobulin G levels were mildly elevated, and antinuclear antibody test was positive at a titer of 1:180. Over the next several years the patient's disease was characterized by moderate exacerbations of arthritis, fever, skin rash, and vasculitic lesion on the fingers and elbows. Her prednisone dose ranged between 10 and 20 mg a day, depending on disease activity, and she was maintained on hydroxychloroquine 200 mg a day. The patient was seen at 2-4 week intervals. On each visit, in addition to routine CBC and urinalysis, blood was drawn for Westergren sedimentation rate and serum complement determination. Immunoglobulin G levels, titer of antinuclear antibodies, and 24-hr urine protein
JOURNALOF ADOLESCENTHEALTHCAREVol. 2, No. 4
quantitation was performed at 3-4 month intervals. On many occasions the patient expressed concern about the side-effects of her medications. She was particularly worried about her cushingoid appearance, an acneiform eruption over the face and arms, and obvious striae over the buttocks, thighs, and lower legs. She was also aware of a slight yellowish tinge to her skin. It was explained to the patient and her parents that these troublesome side-effects would improve significantly when, disease activity permitting, her drug dosages were further reduced. The patient found this counsel to be comforting, and was better able to cope with her disease. Psychological Reactions to the Illness
Following discharge from her initial hospitalization, the patient became increasingly depressed. She indicated particular unhappiness about having to see a doctor on a regular basis and the prospect of having to take drugs indefinitely. The patient was argumentative and short-tempered with friends and relatives and became increasingly disinterested in her school work. When she refused psychiatric help, an aunt with w h o m the patient was particularly close was asked to assist in her emotional support. Her intervention produced a dramatic improvement in the patient's frame of mind. At age 16 years, a family member disclosed that the patient had become increasingly irritable with marked mood swings. A diagnosis of central nervous system lupus was entertained. A careful physical examination failed to reveal neurologic deficits. The patient's cognitive function was intact, and laboratory parameters of disease activity, including Westergren sedimentation rate, serum complement and immunoglobulin G level, were normal. It was felt that the patient's emotional lability represented a functional disorder. She gradually improved without change in her prednisone dose of 10 mg once a day. Compliance
At age 17 years, on a routine visit, the patient for the first time admitted that she was not taking the prednisone as prescribed. She was increasingly concerned about her facial appearance and increased weight. Because of a planned trip to Europe, she was anxious to be more attractive. In spite of admonitions to avoid sun exposure, especially during midday, the patient spent long hours in the sun while in Europe. She noted that following such ex-
June 1982
posure there was a marked increase in rash over the face and she was more easily fatigued by activity. On her own initiative she increased her prednisone dose from 10 to 20 mg a day, and the rash and fatigue improved. The importance of strict drug compliance was continuously stressed to the patient, yet on several subsequent visits she admitted to manipulating her medications. Sexual Concerns
Shortly after her 18th birthday, the patient broached the subject of marriage and the possibility of having children. She was concerned about how her boyfriend might react if he knew fully about her illness. She admitted having sexual relations without contraceptive protection. The patient was informed that birth control pills might exacerbate SLE and that pregnancy might be dangerous unless the disease was under optimal control. She was referred to a gynecologist for contraceptive advice and received instructions on the use of a diaphragm. It was felt that an intrauterine device posed an additional risk as a potential source of infection. Course of the Disease
Five years after her initial hospitalization the patient presented with pleuritic chest pain and was found to have a loud pericardial friction rub. For the first time her urinalysis was abnormal with protein of 1.2 g/24 hr. Urinalysis 2 months before had been normal. Westergren sedimentation rate was now 91 and serum complement level was 70. A renal biopsy disclosed diffuse proliferative glomerulonephritis. In spite of the patient's reservations, her corticosteroid dosage was increased to 30 mg of prednisone a day in divided doses. The pericarditis rapidly resolved and the proteinuria gradually subsided over the next two months. Since that time, the patient's disease had been successfully controlled on 10 mg of prednisone a day in a single dose, and 200 mg of hydroxychloroquine. The patient now has been dealing with her disease with greater equanimity perhaps a reflection of her psychosocial maturation. Her relationship with her parents and siblings has improved significantly.
Discussion The previous case illustrates many problems that may confront the physician treating an adolescent with SLE. The emotional strain of this chronic dis-
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ease is intensified by the potentially disfiguring features of the disease and its treatment. This occurs at a time w h e n body image is fragile and the need for acceptance by peers is peaking. The following physical and emotional aspects of the illness in the adolescent deserve special consideration. Among the physical manifestations of SLE, often the most disturbing to the adolescent are dermatitis, alopecia and vasculitic lesions. The most easily recognized skin lesion is the butterfly eruption. Although it is often photosensitive, it usually heals without scarring. If erythema persists, it can often .be masked by the use of special covering makeup (such as Cover Mark). Discoid skin lesions, which frequently involve the face and scalp, are more dif: ficult to manage. This rash is often scaly and it heals with atrophic areas with varying pigmentation. These scarring lesions are distressing to the adolescent. Fortunately, there is often improvement with local corticosteroid therapy. For many patients exposure to the sun not only exacerbates the skin lesions but it may lead to a generalized increase in disease activity. It is therefore best for these patients to avoid direct sun light. When this is not possible, the use of sun screen agents containing para-aminobenzoic acid (PABA) is advisable (2). The physician often has difficulty dissuading the adolescent patient from going to the beach or sitting by the pool during the summer. A compromise is to have the patient swim at the beginning or end of the day w h e n the sun's rays are less direct. Diffuse hair loss is common in active SLE. Usually the loss of hair is most prominent in the frontal areas. If the alopecia is severe, the patient can avoid embarrassment by using a wig. Vasculitic skin lesions involving the elbows and fingers are also common manifestations o f SLE. In addition to being painful, these lesions may be unsightly. Along with periungual erythema and nail fold infarcts, nail lesions and onycholysis are common (3). The patient can be reassured that hair often grows back w h e n the disease activity lessens, and thatowith proper therapy the skin lesions can be controlled. The adolescent SLE patient soon learns that their chronic disease has a propensity for exacerbations and remissions. Because of this variability in disease activity, assymptomatic patients must be followed regularly with blood and urine studies performed at one to three month intervals. It is not unusual for patients with active r6nal or pleuropulmonary disease to require follow-up at weekly intervals. The adolescent may feel that this significantly interferes
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with some of their school and social activities. More importantly, there is the realization that they are not "'normal" and that their illness sets them apart from their peers. Hall and his associates found that patients who sever social relationships tend to have exacerbations of disease twice as frequently as those who remain socially active (4). Thus it seems important to ensure that the teenager does not become isolated from his or her peers. Klippel and Zvaifler state that, "depression often coincides with the onset of disease or with the institution of adrenal corticosteroid therapy for the systemic features of SLE" (5). The patient described earlier experienced a variety of emotional responses to her disease including periods of depression and episodes of anxiety. As with any chronic illness, the patient may exhibit a wide range of psychological reactions. The intensity of these responses, as Blumen field note s, "will depend on the degree of illness, particular symptoms and of course the psychological make-up of the patients" (6). While depression is not unexpected in a prolonged illness, this disturbance of mental function is particularly common in lupus patients. For the adolescent this is understandable. The disease and the medications used to treat it not only cause marked changes in appearance, but also cause the patient to question whether they will be able to pursue their life goals of work, marriage, and childbearing. Their ultimate fear is that of premature death. Educational counseling by the physician on the course and nature of the disease is important to arrest unfounded fantasies, Efforts must be particularly directed at dispelling the popular myth that the disease is invariably fatal. Because of the frequency of contact and the opportunity to develop personal rapport, the primary care physician is the most important source of psychiatric support. More structured psychiatric intervention is advisable if the patient develops severe depression, psychotic episodes, or has suicidal tendencies. It is particularly important for the physician to distinguish these psychological reactions from true central nervous system involvement. SLE is somewhat unique in that involvement of the central nervous system is a frequent part of the disease process. It is usually characterized by disturbances in mental function (5). Organic psychiatric syndromes have been reported in as many as 42% of patients with SLE (7). There is evidence that both vascular and immune mechanisms are involved in its pathogenesis (8). As pointed out by Guze (9), there is a remarkable variability in the clinical picture of SLE
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induced psychiatric illness. The organic syndromes reflecting cerebritis or ence~0halitis are often characterized by impaired cognitive function, i.e., changes in orientation, memory, or perception (5). This is the most serious form of neurologic disease and requires high-dose corticosteroid therapy. Patients with nonorganic syndromes usually have normal cognitive function. The most common functional disorder is depression, often characterized by emotional lability, insomnia, and spontaneous crying (4). These individuals usually respond to reassurance and family support but at times may also require psychotherapy. Since SLE patients often require significant doses of corticosteroids for protracted periods of time, the physician must be familiar with the common sideeffects: facial mooning, weight gain, edema, hypertrichosis, ecchymotic lesions, acne, and striae. These features are understandably distressing to the adolescent w h o is sensitive to changes in body image. In some instances, high doses of corticosteroids result in the cessation of menstrual periods. In addition, corticosteroid therapy itself may be complicated by serious psychological disturbances (10). This is particularly true with the high dosages (11). While there is no way of predicting which patients will have a psychological reaction to corticosteroids, those individuals with known psychological problems experience more frequent and more serious disturbances (12). Another potential consequence of corticosteroid therapy is the development of significant osteoporosis. This takes on added significance when one considers the metabolic needs of the growing adolescent. Recently it has been shown that there are reduced serum levels of 1,25-(OH)2 vitamin D3 in prednisone-treated adolescents with SLE (13). As a consequence, these patients may require supplemental vitamin D. The physician should encourage the patient to be physically active since this may retard osteoporosis and enhance the feeling of wellbeing. SLE patients with arthritis or skin rash can usually be satisfactorally managed with antimalarial and anti-inflammatory drugs. But corticosteroids may be required on an intermittent basis and should be used in the lowest possible dose sufficient to suppress the disease. Westergren sedimentation rate, i m m u n o globulin G and serum complement levels are the most useful laboratory parameters for assessing disease activity. Reduction in serum complement may antedate exacerbation of disease by months (14). Physical examination and serologic measurements
June 1982
are both important in determining corticosteroid dose. However, isolated laboratory, abnormalities are not a justification for changing amounts of medication. At times an alternate day schedule of corticosteroid administration is effective in controlling SLE and may ameliorate the manifestations of Cushing's syndrome (15). Yet, while most of the side-effects of corticosteroids can be avoided with alternate day doses, this regimen is often ineffective in controlling SLE, particularly w h e n there is renal, cardiac, or central nervous system involvement. Patients taking prednisone on a daily basis can expect to lose the moon facies, once it has developed, only after the dose is reduced to between 5 and 10 mg a day, The patient requires repeated reassurance from the physician that the changes associated with corticosteroid therapy will regress w h e n the dosage is eventually lowered. Another drug commonly used in the management of skin rash and the arthritis associated with SLE is the antimalarial agent hydroxychloroquine. It is generally given in a dose of between 200 and 400 mg a day. The major side-effect of this drug is retinal toxicity. However, with regular ophthalmologic examinations and visual field testing repeated at 6-month intervals, hydroxychloroquine may be safely used (16). The physician must be alert to the fact that this drug may on occasion cause irritability, emotional changes, nightmares, and even psychosis (17). In addition it may induce alopecia, yellowish pigmentation of the skin, bleaching of the hair, and a variety of skin eruptions which may be confused with the dermatologic manifestation of SLE. However, these toxic reactions are rare if the dose is kept at 400 mg or less a day. As with corticosteroids, the side-effects of this medication generally regress with a lower dose, i.e., 200 mg every other day. Of particular concern to young w o m e n with SLE is the affect the disease may have on their ability to bear children. They often w o n d e r if the child will inherit the disease. The patient should be reassured that having SLE does not preclude child bearing, but that pregnancy does entail some increased risks for both mother and child particularly w h e n the disease is active. The association of certain B-cell alloantigens with SLE suggests that genetics does play a role in the etiology of this disease (18). Therefore, a child of an SLE mother may be at additional risk to develop the disorder, but this rarely occurs. If the adolescent patient with SLE is sexually active, she should be made aware of the potential for the pregnancy or an abortion to cause a serious flare
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in the disease. In addition, a young women with a chronic disease may find child care unduly stressful, In general, it is best to defer pregnancy until th.e disease is under good control (19). The question of contraception is a delicate topic for discussion between physician and adolescent. Since birth control pills may cause a lupus-like diathesis or a flare in preexisting SLE disease, it is best to avoid these agents and to recommend another form of contraception. At times it may be difficult for the adolescent to decide which is more disturbing, the lesions as.sociated with SLE or the side-effects of the medications used. Not infrequently the patient will secretly reduce the dose of corticosteroid to avoid being cushingoid. The physician must be alert to this and should emphasize to the patient •the serious consequences that may ensue from inadequately controlled disease. As James Masterson writes, adolescence !s "a stage in individual growth and development which has been notorious throughout the centuries as One of great emotional upset with wide fluctuations in behavior" (20). Add to this milieu a disfiguring disease, one can readily understand the potential for psychological disturbances. The physician plays a primary role in helping the patient cope with the disease. Adolescents require constant support in interpreting how the disease is affecting them as individuals, rather than textbook discussions of the illness. It is essential that the family be involv.ed early in this process. The parents often have a difficult task. On one hand they must not allow the child to develop undue dependence and should encourage her to live a productive life without indulgence in self pity. On the other hand, parents have to assure that medications are taken correctly and that proper limitations of stressful activities are observed. Patients may t ~ to assert their independence by manipulating their medications or by attempting to function on the same level as their peers. However, with reassurance and emotional support appropriate for the patient's age, the adolescent with SLE°can usually withstand the vicissitudes of the illness and successfully negotiate t h e psychological and social developmental tasks of adolescence.
References 1. Rothfield N: Clinical features of systemic lupus erythematosus, in KellyWN, Harris ED, Ruddy S, et al. (eds):Textbook of Rheumatology. Philadelphia, W.B. Saunders, 1981, pp. 1106,1132.
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2. Furey NL, Esterly NB: Lupus erythematosus. Major Prob Clin Pediatr 19:367-403,1978. 3. Urowitz MB, Gladman DD, Chalmers A, et al.: Nail lesions in systemic lupus erythematosus. J Rheumatol 5:441-447, 1978. 4. Hall RCW, Stickney SK, Gardner ER: Psychiatric symptoms in patients with Systemic lupus erythematosus. Psychosomatics 22:15-24,1981. 5. Klippel JH, Zviafler NJ: Neuropsychiatric abnormalities in systemic lupus erythematosus. Clin Rheum Dis 1:621-638, 1975. 6. Blumenfield M: Psychological aspects of systemic lupus erythematosus. Primary Care 5:159-171,1978. 7. Estes D, Christian CL: The natural history of systemic lupus erythematosus by prospective analysis. Medicine 50:85-95, 1971. 8. Bresnihan B, Hohmeister R, Cutting ], et al.: The neuropsychiatric disorder in systemic lupus erythematosus: Evidence for both vascular and immune mechanisms. Ann Rheum Dis 38:301-306,1979. 9. Guze SB: The occurrence of psychiatric illness in systemic lupus erythematosus. Am J Psychiatry 123:1562-1570,1967. 10. Carpenter WT Jr., Bunney WE Jr.: Effects of cortisol in man. Seminars Psychiatry 3:421-434,1971. 11. The Boston Collaborative Drug Surveillance Program: Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 13:694-698,1972.
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12. Williams GH, Dluhy RG, Thorn GW: Diseases of the adrenal cortex, in Isselbacher KJ, Adams RD, Braunwald E, et al. (eds): Harrison's principals of internal medicine. New York, McGraw HiII, 1980, pp. 17!1-1736. 13. O'Regan S, Chesney RW, Hamstra A, et al.: Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand 68:109-111,1979. 14. Singsen BH, Bernstein BH, King KK: Systemic lupus erythematosus: C~rrelations between changes in disease activity and serum complement levels. J Pediatr 89:358-365,1976. 15. Axelrod L: Glucocorticoid therapy. Medicine 55:39-65,1976. 16. Rynes RI, Krohel G, Falbo A, et al.: Ophthalmologic safety of long-term hydroxychloroquine treatment. Arthr Rheum 22:832-836,1979. " 17. Dubois EL: Systemic lupus erythematosus: Recent advances in its diagnosis and treatment. Ann Intern Med 45:163-184, 1956. 18. Reinertsen JL, Klippel JH, John AH, et al.: B-lymphocyte alloantigens associated with systemic lupus erythematosus. N Engl J Med 299:515-518,1978. 19. Steinberg AD: Management of systemic lupus erythematosus, in Kelly WN, Harris ED, Ruddy S, et al. (eds): Textbook of Rheumatology. Philadelphia, W.B. Saunders, 1981, pp. 1133-1150. 20. Masterson JF Jr.: The psychiatric dilemma of adolescence. Boston, Little, Brown Co., 1967.