ChloroquineV1, Istex, Corpus, bibRecord, 001578

Review: Lupus in adolescence

Identifieur interne : 001578 ( Istex/Corpus ); précédent : 001577; suivant : 001579

Review: Lupus in adolescence

Auteurs : I. Kone-Paut ; M. Piram ; S. Guillaume ; T. A. Tran

Source :

Lupus [ 0961-2033 ] ; 2007-08.

RBID : ISTEX:DB244ED8ECE0108609E36C3A428F9882408CD7AB

English descriptors

Teeft :
- Adult care, Adult patients, Anticardiolipin antibodies, Antiphospholipid, Antiphospholipid antibodies, Antiphospholipid syndrome, Arch pediatr, Arthritis, Arthritis rheum, Best pract, Cell transplantation, Childhood onset, Chronic disease, Chronic illness, Clinical change, Disease activity, Disease course, Disease damage, Disease duration, Disease exacerbations, Disease onset, Erythematosus, Gonadal function, Health care, High titres, Immunosuppressive agents, Irreversible damage, Jsle, Jsle patients, Juvenile idiopathic arthritis, Life expectancy, Lupus, Lupus anticoagulant, Lupus erythematosus, Lupus lupus, Lupus nephritis, Main causes, Major concern, Malar rash, Monoclonal antibodies, Mood swings, Mycophenolate mofetil, Organ damage, Osteoporosis, Ovarian failure, Overall prognosis, Paediatric, Pediatr, Pediatric, Physical activity, Physical changes, Psychosocial development, Relevant questions, Renal disease, Rheum, Rheumatol, Steroid, Successful transition, Syndrome, Systemic, Systemic lupus, Systemic lupus activity measure, Systemic lupus erythematosus, Systemic lupus erythematosus disease activity index, Therapeutic approaches, Weight loss, Young patient.

Abstract

Juvenile systemic lupus erythematosus (JSLE) represents 15—20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care. Lupus (2007) 16, 606—612.

Url:

https://api.istex.fr/ark:/67375/M70-Q1N6CHVB-X/fulltext.pdf

DOI: 10.1177/0961203307079562

Links to Exploration step

ISTEX:DB244ED8ECE0108609E36C3A428F9882408CD7AB

Le document en format XML

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<abstract xml:lang="en"><p>Juvenile systemic lupus erythematosus (JSLE) represents 15—20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care. Lupus (2007) 16, 606—612.</p>
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<journal-title>Lupus</journal-title>
<issn pub-type="ppub">0961-2033</issn>
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            <publisher-name>Sage Publications</publisher-name> 
            <publisher-loc>Sage UK: London, England</publisher-loc> 
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<article-meta><article-id pub-id-type="doi">10.1177/0961203307079562</article-id>
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<title-group><article-title>Review: Lupus in adolescence</article-title>
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         <contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Kone-Paut</surname>
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<aff>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France, <email xlink:type="simple">isabelle.kone-paut@bct.aphp.fr</email>
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         <contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Piram</surname>
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<aff>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</aff>
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         <contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Guillaume</surname>
<given-names>S.</given-names>
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<aff>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</aff>
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         <contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Tran</surname>
<given-names>T.A.</given-names>
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<aff>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</aff>
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         <pub-date pub-type="ppub"><month>08</month>
<year>2007</year>
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<volume>16</volume>
<issue>8</issue>
<issue-title>Special Issue: Pediatric Lupus; Guest Editor: Rolando Cimaz</issue-title>
<fpage>606</fpage>
<lpage>612</lpage>
<abstract><p>Juvenile systemic lupus erythematosus (JSLE) represents 15—20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care. <italic>Lupus</italic>
 (2007) <bold>16</bold>
, 606—612.</p>
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<meta-value>606 ReviewLupus in adolescence SAGE Publications, Inc.200710.1177/0961203307079562 I.Kone-Paut Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France, isabelle.kone-paut@bct.aphp.fr M.Piram Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France S.Guillaume Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France T.A.Tran Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France *Correspondence: Isabelle Koné-Paut, Department of Paediatrics and Paediatric Rheumatology, CHU de Bicêtre, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France. Juvenile systemic lupus erythematosus (JSLE) represents 15—20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care. Lupus (2007) 16, 606—612. damage juvenile systemic lupus erythematosus management of treatment transition Introduction Systemic lupus erythematosus (SLE) affects 50 to 100/100 000 persons in the United States and Europe, with racial and geographic variations.1 The disease onset during childhood and adolescence represents 15–20% of cases, higher rates being reported in females between 12–16 years. In comparison to adult- SLE, the course of juvenile SLE (JSLE) has been reported more severe with higher frequency of aggres- sive renal disease and higher requirement for steroids and immunosuppressive drugs.2–5 The prognosis of SLE has improved from less than 50% five-year sur- vival in 1955, to more than 90% 10-year survival in the more recent studies.6–9 The dramatic improvement of life expectancy is attributable to earlier diagnosis, recognition of milder forms and more accurate man- agement of treatment. Consequently, juvenile patients with SLE are at high risk for entering adulthood with their disease related-morbidity, damage and disability. Recent studies, using the systemic lupus international collaborating clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI), and the child health related quality of life (CHQ), showed sig- nificant rate of overall SLE-related damage (40%) occurring early in the course of disease and affecting especially the renal, musculoskeletal and neuropsychi- atric domains of the SDI.8,10,11 A modified paediatric version of the SDI, evidenced also significant addi- tional growth failure (15.3%) and delayed puberty (11%), running in parallel with the increase of disease duration.11 Considering its overall outcome, JSLE remains a serious and devastating disease. Physicians involved in the care of these adolescent patients have to overcome a summation of challenges coming from the severity of the disease per se, the cumulative treatment toxicity, and the psychosocial consequence of a chronic illness that happens during a time of profound physical, emotional and social changes. Moreover, care providers will have the difficult task of a successful transition process of their adolescents to an adult lupus clinic. Clinical characteristics of JSLE The presentation, clinical symptoms and biologic find- ings of adolescents with JSLE resemble those of adult patients. 607 Initial presentation Patients affected with JSLE originate from families with increased prevalence of frequency of SLE and other autoimmune diseases. The median age of onset of disease is 10–12 years, with 85% of cases starting after the age of eight years. The median age for diag- nosis ranges from 12 to 14 years, with a progressive trend with time to recognize the disease earlier. Females are affected three to five times more than males.12–14 Patients with JSLE may present with con- stitutional symptoms (fatigue, myalgia, fatigue, weak- ness, weight loss), skin rashes, especially malar rash and arthralgia/arthritis that may precede the detection of organ-specific lesion. The high frequency (30–50%) of severe renal disease (stage III or IV of the WHO classification) at JSLE presentation differs from adult- SLE, and is a strong indicator for morbidity and mortality.12–16 The occurrence of non-classical mani- festations is not exceptional (16%), especially severe gastrointestinal features such as peritonitis, pancreati- tis, mesenteric vasculitis and occlusion.12,17 Much more unusual presentations may include haemolytic and uremic syndrome or macrophage activation syndrome.12,18 Biological findings Serum inflammatory markers show a frequent discrep- ancy between the erythrocyte sedimentation rate (ESR) value (markedly elevated) and the C-reactive protein (CRP) value (normal or slightly elevated), except in cases of concomitant serositis or infections.19,20 This finding in association with a decreased leukocyte count is a helpful tool for the diagnosis of SLE in a young patient. The immunological characteristics of JSLE are similar to those of adults, with positive ANA (70% of cases with titres > 1 : 640) and positive anti-dsDNA in more than 90%. The association of lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL) reaches 29% and 47% respectively. Challenges for early recognition of SLE in an adolescent Some adolescent patients experience long periods of illness before they receive appropriate treatment. Indeed, the leading presenting symptoms of JSLE are not specific. An adolescent with fatigue, headaches, weight loss, mood swings and weakness will rather be considered having depression, anorexia nervosa or chronic fatigue syndrome than having lupus. Some of them may undergo unnecessary diagnostic procedures or inaccurate referral to a psychiatrist. Additional deleterious consequences of a long diagnostic delay include prolonged difficulties in their learning activities and a significantly increased risk of organ involvement and damage. Some JSLE patients may be initially diagnosed with another disease such as juvenile idiopathic arthritis, immune-mediated throm- bocytopenia or anaemia, antiphospholipid syndrome, and may develop complete SLE after several months or years. The detection of high titres of ANA in these patients requires careful and long-lasting follow-up for detection of other features of SLE. Clinical course During the evolution, JSLE patients develop more frequently malar rash, neurological features (headaches, chorea, seizures) and renal disease than adult patients. The frequency of other main features of SLE is equal to that in adult SLE.2,3,5 While the evolu- tion of the disease is highly variable, it has been shown that haematological and renal disease are worse in JSLE than in adult SLE. These threatening involve- ments often require high-dose steroids and immuno- suppressive drugs to avoid irreversible damage. Conversely, these theoretically disease-beneficial treat- ments lead to considerable toxicity. The disease activity cannot be measured directly by clinical and biological examination. To optimize the treatment of individual patients, standardized and reproducible scores have been designed for better evaluation of disease activity and response to treatment. SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), BILAG (British Isles Lupus Assessment Group), and SLAM (Systemic Lupus Activity Measure) have been demon- strated to be highly sensitive to clinical change in patients with JSLE.21,22 The use of these instruments is highly recommended to avoid under and over- treatment of JSLE patients, which are both deleterious for patient's health and quality of life. Outcome and mortality The overall prognosis of JSLE has markedly improved during the last two decades because the diagnosis is made earlier and because there are new therapeutic approaches, the most recent of them tending toward disease eradication.23,24 The best indicator of prognosis improvement is the constant reduction of mortality, which actually rarely exceeds 10% after a mean disease course of 10 years.6–8 The main disease-related causes of death are acute cardiovascular and haematological events, most of them occurring in patients with chronic renal failure. Other causes of death, in particular those related to treatment, are accelerated cardiovascular disease and infections. Secondary neoplastic diseases such as non-Hodgkin's lymphoma and lung cancer, reported as causes of death in adult SLE, are poorly 608 reported in the course of JSLE.8 In contrast to what previously thought, gender and race are not related to disease outcome and death in the paediatric populations with lupus. Management of treatment The management of adolescents with SLE has to overcome the three main challenges of controlling the disease, obtaining patient's adhesion to treatment and preventing the damages induced by secondary effects of medications. Mild skin and joint manifestations may be controlled by NSAIDS and hydroxychloro- quine, which also has a lipid-lowering effect and may stabilize aPL-linked thrombopenia.25–27 As JSLE is often an aggressive disease, the requirement for high- dose steroids may be sustained. The consequences of such treatment are considerable and may impact directly in all fields of the adolescent physical and psy- chosocial development. Physical changes including obesity, stunted growth, delayed puberty, striae and hirsutism are the main fears of these patients experi- encing complex developmental process. Giving that during adolescence the risk of misunderstandings in care relationships is much higher than during the other life periods, a significant percentage of patients (about 50%) will not follow accurately their treatment pre- scription.28 Less visible secondary effects, i.e., osteo- porosis and premature atherosclerosis, are also a major concern for their future quality of life and life expectancy. By now there is no recommendation for the use of immunosuppressive agents, and currently they are initiated when there is a significant risk of organ damage (eg, in the presence of biopsy-proven diffuse glomerulonephritis or acute CNS disease). In other situations of prolonged steroid requirements with doses >0.3 mg/kg/day and in case of steroid dependence, they should also be highly recommended. The choice for the type of immunosuppressant is not standardized. Given its good tolerance and its ease of use in adolescents, azathioprine has often been the first choice. In most cases, azathioprine facilitates steroid tapering and allows the maintenance of disease control after courses of cyclophosphamide. The direct effect of this drug on disease activity has not been demon- strated. In addition to steroids, mycophenolate mofetil (MMF, Cellcept®) has been proven as effective as cyclophosphamide for inducing remission in adult SLE patients with diffuse proliferative glomeru- lonephritis, with no significant difference in the rate of relapses and less infectious events.29 There is no similar study performed in JSLE patients, but reports suggest that MMF is not regularly effective in stage IV lupus nephritis.30 The use of cyclophosphamide in adolescents, even if mandatory in threatening organ flares, can induce serious immediate and long-term toxicities. The most common, nausea, GI discomfort, hair loss, and the necessity of hospitalization for heavy monitoring are very restricting for these young patients. The most severe, life-threatening infections, ovarian failure, and the increased risk of secondary neoplasia, may lead to patient/parents refusal of this treatment. During the past two years, new B-cells tar- geted monoclonal antibodies (Rituximab) have been used successfully for treatment of refractory immuno- logic cytopenia and for severe renal disease in JSLE patients. Apparent clinical and biological eradication of SLE was observed in a significant number of cases, some of which experienced prolonged remission (six months to two years) concomitant with B-cells deple- tion.23,24 The results in terms of tolerability remain still controversial, but the number of treated patients is actually too low. Autologous stem cell transplantation has been performed in a cohort of 50 adult patients with SLE with satisfactory results in terms of complete remission and low treatment-related mortality (4%); however, the experience is very limited in JSLE.31 New tools are becoming available for immunomodula- tion, eg, other anti-B-cell agents such as anti-CD22, anti-BAFF (a cytokine playing a major role in autore- active B-cell survival), toleragen molecules specific for autoreactive B-cells (LJP394), and peptide vaccina- tion. The most encouraging aspect of these results and perspectives is the possibility to use new drugs that are more effective, less toxic and have a longer effect than conventional steroid and immunosuppressive treatments. Management of the antiphospholipid syndrome The presence of persistent circulating antiphospholipid antibodies (aPL), such as lupus anticoagulant (LAC) and high-titre anticardiolipin antibodies (aCL) is common in JSLE patients (up to 40% and 80%, respec- tively). The antiphospholipid syndrome (APS) has protean manifestations, that in children include prima- rily immunologic thrombocytopenia and anaemia, recurrent venous and arterial thrombosis, and CNS manifestations (stroke, chorea). Venous thromboses are more commonly reported than arterial ones, that occur mostly in young children. Livedo reticularis, heart valve disease and pulmonary involvement are less common in children compared to adults.32 The risk of developing thrombosis is thought to be high in JSLE patients who either have developed a first thrombotic event or have high titres of aCL.33 In these cases, rigor- ous preventive anticoagulation following an interna- tional normalized ratio (INR) between 2.5–3.5 is highly recommended. For other patients with low or moderate 609 levels of aCL, no clinical symptom, and no previous episode of thrombosis, prophylaxis with low-dose aspirin may be sufficient, even if there is no clinical study showing any advantage of this course of treat- ment for preventing further clinical events. Damage in juvenile SLE The frequency of irreversible damage is high in JSLE and involves especially the renal, musculo-skeletal and neuro-psychiatric domains of the SDI. Recently a modified version of the SLICC/SDI score was applied to a wide multicentric population of 1015 patients from 39 countries and retrieved 10.1% of nephrotic- range proteinuria, 5.9% of cataract, 5.6% of cognitive impairment or major psychosis, 4.5% of muscle atro- phy or weakness, 4% of scarring alopecia, 3.7% of avascular bone necrosis and seizures respectively. Most of them occurred within the first year of dis- ease.11 In addition to these, two parameters of transient damage, delayed puberty and growth failure were calculated at 11.3% and 15.3% respectively. They increased with disease duration, especially after the fifth year. These disease/treatment related damages need to be carefully monitored and, as much as possi- ble, need to be early prevented in patients with JSLE, especially in those with high cumulative disease activ- ity and steroid use.34 Osteoporosis Osteoporosis in JSLE is the result of cumulative effects of chronic inflammation, pubertal delay, renal failure, sustained steroid intake and voluntary decreased sun exposure. The consequences on bone mass index (BMI) are considerable because, in healthy children, the BMI increases by 40% during puberty and the theoretical age for reaching the peak of bone mass is 18 years. A study of 70 JSLE patients with a mean disease duration of 10.8 ± 8.3 years, has reported a significant decrease of BMD (measured by dual X-ray absorptiometry) at the lumbar spine in JSLE patients compared to age and sex-matched controls.35 Decreased BMD was correlated with male sex and cumulative steroid use. The prevention of osteoporosis implies both optimal disease control and steroid economy. In steroid-dependent patients, the use of the lowest possible doses may be helped by alternative immunosuppressive therapy. Adjunctive measures include a balanced diet, calcium and vitamin D supplementation, and maintenance of physical activity. The use of biphosphonates in severe sympto- matic osteoporosis may be needed for pain relief especially in case of vertebral collapses. These drugs are currently effective, do not affect linear growth and are well tolerated, even if they may induce mild flu-like symptoms and hypocalcaemia. The use of biphosphonates for optimal bone loss prevention in children is still controversial because the long-term effects related to their sustained fixation in a growing bone are not known. Another important subject of dis- agreement is the possible extra-skeletal deposition of these molecules and their either protective or aggravat- ing consequences on atherosclerosis, a major concern in SLE patients.36,37 Risks to fertility, ovarian failure The gonadotoxic effects of cyclophosphamide are well known, and it is usually considered that post-pubertal women having received a cumulative dose over 12 g are at risk of premature ovarian failure (POF). There are only few data on gonadal function in patients with JSLE. A three-year cohort study regarding the gonadal function in adolescents with SLE had shown that, while the occurrence of overt POF was very rare, 30% of the young females had significant decrease of their ovarian reserve, especially those exposed to a mean dose of 21 g of cyclophosphamide.8 Therefore these women may encounter conception difficulties and POF in their future. Male adolescents with SLE have a higher risk to fertility than females. The decision of starting treatment with cyclophosphamide needs prior thorough evaluation and explanation of the risks and benefits to the patients. Sperm banking should be offered for post pubertal males after careful discussion. Cardiovascular outcome Besides cancer and infections, acute cardio-vascular events linked to atherosclerosis are the leading cause of death in both adult and juvenile SLE. While cardio- vascular events appear late in the course of the disease, the progression of atherosclerosis is early accelerated. This phenomenon is the direct consequence of SLE as a result of combined inflammatory, immunologic and endothelial dysfunction, and is also linked to the meta- bolic effects of sustained corticoid use (hypercholes- terolemia, dyslipidemia, obesity). Reasonable strategies to reduce the risk of atherosclerosis include treatment of hypertension and hyperlipidemia, avoid- ance of tobacco smoking, promotion of physical activ- ity and weight control. Antimalarial drugs may prevent against lipid vascular deposition. Issues on health-related quality of life As the chance for survival increases with time, the impact of chronic disease and treatments on 610 health-related quality of life (HRQL) becomes a major concern in patients with JSLE. A recent study investi- gating the CHQ in 297 JSLE patients has shown that they had poorer HRQL as compared with healthy con- trols in both physical and psychosocial domains.10 Renal and musculoskeletal damage were the most frequent variables influencing the physical health. As compared with patients with juvenile idiopathic arthritis, JSLE patients experienced less pain but lower self-esteem and worse parents' assessment of overall health and illness. As the HRQL is directly related to organ damage, finding more effective and less toxic treatment regimen is mandatory to improve patients' quality of life. Adjunctive therapies are also critical for early prevention of short stature and osteoporosis. Relevant questions concerning SLE in adolescence Signs and symptoms of the disease Both visible and invisible signs of SLE itself, and consequences of treatment, may alter deeply the adolescent self-esteem and his relationships with other adolescents. Persistent headaches, mood swings and cognitive difficulties may impair seriously their learn- ing skills. The significance of headaches, a frequent symptom in adolescence and in SLE, may be an enigma for the physician. Worsening symptoms should lead to reassessment of disease activity, but even modern imaging techniques often fail to evidence organic brain lesion in this situation.38,39 Physical changes induced by steroid use in girls such as obesity, hypertrichosis, striae constitute intolerable stigmata often more stress- ful than the disease itself. Others restrictions in terms of diet, oral contraception, sun avoidance and alcohol and tobacco use may accelerate their social exclusion. The adolescent needs to be reassured that these con- cerns are being taken seriously. Personal educational planning providing comprehensive explanations on the effects of disease and treatment must be negotiated with the team in charge of the patient. The inputs from a nutritionist and a psychologist experienced in dealing with these specific problems may be helpful.28,38 Adhesion to treatment The adolescent will search progressively to manage his health care by his or her own. To satisfy this goal, he will expect his physician to involve him directly in decision-making regarding his treatment, whatever is the parents' point of view. Questions regarding inti- macy, confidentiality and role distribution in treatment execution may be potential source of difficulties. An important point to remember is that in all ages compliance, exceptionally total or absent, follows a current scheme `in between.'28 The best guarantee for treatment adhesion is to spend appropriate time with the adolescent explaining the goals and risks versus benefits of medications. Steroid treatment, often devastating to teenage girls, needs to be regularly rene- gotiated, especially for schedule accuracy and to avoid premature discontinuation. Sexual health and fertility SLE may result in delayed pubertal development. During active lupus, adolescent girls have frequent amenorrhoea or irregular menses, making them fear that this will be associated with infertility. It is not proven that JSLE patients have sexual activity later than their healthy peers.28 The necessity for oral or subcutaneously implanted contraceptives may be pre- cipitated by hemorrhagic events, which are favoured by severe thrombopenia or co-medications with anti- coagulants. Therefore, contraception must be dis- cussed as soon as possible with JSLE adolescents, as possible independently from their parents. Cyproterone acetate (Androcur®) and chlormadinone acetate (Luteran®) are suitable products to utilize in this context. Contraceptive methods are detailed else- where in this issue (see pages 600–605, Tincani et al.). The risks related to pregnancy (fetal loss, disease flare, thrombo-embolic events and neonatal heart block) must be explained, but with the assurance that concep- tion is possible under careful medical assistance. Transition from paediatric to adult care The transition from paediatric to adult-oriented health care should happen in the context of the main develop- ment stages that characterize adolescence: being comfortable with their developing body and sexuality, moving toward independence from their parents, face the future and make important decisions about their education, careers and goals.28 The process of acquisi- tion of these developmental tasks is severely impaired in adolescents facing a chronic disease like SLE. Four partners are the main actors of the transition process: the patient, the parents, the adult-care provider and the paediatrician. It is evident that each of them encounters psychological and emotional barriers that may com- promise the task of a successful transition. The young patient fears his disease and its future consequences on quality of life and lifespan. He may not be willing to leave the protective environment of the paediatric 611 clinic where care priorities are focussed on growth, development and family problems, to the adult one where the main priorities will be focused on social independence, professional tasks and reproduction problems. Parents, who have positively accompanied their children with the agreement of their pediatric doctor, fear total exclusion in the relationship with an adult. Moreover, they do not believe in their adoles- cents' ability of total independence. The paediatrician has progressed through a long and complex process from the diagnosis to all steps of treatment and follow- up, with gradual adjustment of his relationship to his patient. Moreover his scientific interest to the outcome of the disease may tempt him to prolong the patients' care in the paediatric clinic. The adult rheumatologist has the challenge of integrating a complex medical story and the emotional expectations of his young patient and family.28,40 All these considerations under- line the absolute necessity of a suitable period of preparation for transition with the paediatric team. Different options, depending of medical resources, may include adult consulting in the pediatric clinic, and alternate or shared consults between adult and paediatric doctors. Conclusion As efficiency of treatments and lifespan expectancy improve, JSLE remains a serious disease that may compromise definitely the adolescent's development and quality of life. Most patients require intensive medical treatment, with strict monitoring of potential side effects and impact on global health status at this period of crucial physical and emotional changes. References Houghton KM, Page J., Cabral DA et al. Systemic lupus erythematosus in the pediatric North American native population of British Columbia. J Rheumatol 2006; 33: 161—163. Tucker LB, Menon S., Schaller JG, Isenberg DA Adult and childhood-onset systemic lupus erythematosus: a comparison of onset, clinical features, serology and outcome. Br J Rheumatol 1995; 34: 866—872. Carreno L., Lopez-Longo FJ, Monteagudo I. et al. Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus. Lupus 1999; 8: 287—292. Costallat Ltl , Coimbra Amv. Systemic lupus erythematosus: clinical and laboratory aspects related to age at disease onset. Clin Exp Rheumatol 1994; 12: 603—607. Font J., Cervera R., Espinosa G. et al. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 1998 ; 57: 456—459. Doria A., Iaccarino L., Ghiradello A. et al. Long-term prognosis and causes of death in systemic lupus erythematosus . Am J Med 2006; 119: 700—706. Bernatsky S. , Boivin JF, Joseph L. et al. 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<name type="personal"><namePart type="given">I.</namePart>
<namePart type="family">Kone-Paut</namePart>
<affiliation>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France,</affiliation>
<affiliation>E-mail: isabelle.kone-paut@bct.aphp.fr</affiliation>
</name>
<name type="personal"><namePart type="given">M.</namePart>
<namePart type="family">Piram</namePart>
<affiliation>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</affiliation>
</name>
<name type="personal"><namePart type="given">S.</namePart>
<namePart type="family">Guillaume</namePart>
<affiliation>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</affiliation>
</name>
<name type="personal"><namePart type="given">T.A.</namePart>
<namePart type="family">Tran</namePart>
<affiliation>Department of Pediatrics and Pediatric Rheumatology, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France</affiliation>
</name>
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<abstract lang="en">Juvenile systemic lupus erythematosus (JSLE) represents 15—20% of all SLE cases. The leading presenting symptoms of JSLE are constitutional and not specific such as fatigue, headache, weight loss or mood swings. They are also encountered in healthy adolescents, which explains frequent diagnosis delay. The frequency of irreversible damage is high in JSLE and involves especially the renal, musculoskeletal and neuropsychiatric systems. Although the overall prognosis has markedly improved, thanks to earlier diagnosis and new therapeutic approaches, cardiovascular, hematological events and chronic renal failure remain severe, and constitute the main disease-related causes of death. Treatment is based on hydroxycloroquine and corticosteroids. Immunosuppressive agents must be discussed to decrease the duration of corticosteroids use. New drugs and monoclonal antibodies targeting B-cells and B-cell related cytokines are being evaluated with encouraging results. Management of JSLE has to challenge three objectives: controlling disease progression, obtaining patient's adherence to treatment, and preventing consequences of medication side effects on growth, puberty, development and fertility. Patients' quality of life and psychosocial development have also to be taken into account, as well as the organization of a successful transition from paediatric to adult care. Lupus (2007) 16, 606—612.</abstract>
<subject><genre>keywords</genre>
<topic>damage</topic>
<topic>juvenile systemic lupus erythematosus</topic>
<topic>management of treatment</topic>
<topic>transition</topic>
</subject>
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<identifier type="ISSN">0961-2033</identifier>
<identifier type="eISSN">1477-0962</identifier>
<identifier type="PublisherID">LUP</identifier>
<identifier type="PublisherID-hwp">splup</identifier>
<part><date>2007</date>
<detail type="title"><title>Special Issue: Pediatric Lupus; Guest Editor: Rolando Cimaz</title>
</detail>
<detail type="volume"><caption>vol.</caption>
<number>16</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>8</number>
</detail>
<extent unit="pages"><start>606</start>
<end>612</end>
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Review: Lupus in adolescence

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