Resources See after section Juvenile idiopathic arthritis: overview References Oen K, Malleson PN, et al. Disease course and outcome of juvenile rheumatoid art hritis in a multicentre cohort. J Rheumatol 2002; 29: 1989 \200\22399. \200 Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007; 369: 767 \200\22379. Investigations Laboratory As in the adult form, anemia of chronic disease, neutro- philia, thrombocytosis, and raised in \202 ammatory markers are hallmarks of the disease. \200 \200 See also Juvenile idiopathic arthritis: overview Urinalysis, U&E, LFT should be normal. ANA, ENA, dsDNA are negative and help to distinguish RF + Poly-JIA from autoimmune connective tissue diseases, all of which may be RF positive. This page intentionally left blank SYSTEMIC ONSET JIA 362 Systemic onset JIA \200 \200 \200 This life-threatening condition may be triggered by changes in medicat ion or viral infection. All types of JIA have both arthritis and the risk of joint destruction in common, but it is the extra-articular mani- festations of systemic onset JIA arthritis, which makes it uniqu e. Systemic onset JIA makes up 5 \200\22310% of all JIA. George Frederick Still described t he disease as a distinct entity in children in 1897 (Still, 1897). Hemoglobin, WBC, platelets fall. ESR is elevated. Increased triglycerides and liver transam inases. Extremely high ferritin. Classi \201 cation and diagnosis See under Juvenile idiopathic arthritis: overview Secondary amyloidosis Rare if in \202 ammation controlled. Epidemiology Incidence varies from 0.49 \200\2231.3 per 100 000 children at risk. There is some evidence that incidence is decreasing, and some evidence of seasonality (peaking in sp ring and autumn) suggesting an infectious trigger, but this is by no means clear. \200 Joint pathology High probability of arthroplasty in chronic severe form (57% after 10 years follow-up). Synovial cysts occur more commonly than other forms of JIA and lymphodema of u nknown cause may occur. Investigations Routine laboratory tests, serology and speci \201 c imaging is important wh ere Systemic-onset JIA is being considered. The disease is equally common in males and females, with an average age of onset of 5 years , but wide variability. Systemic onset JIA occurs in all ages and in adults is termed \200 \230adult onset Still disease \200\231. Abnormal results from investigations arranged when considering a diagnosis of systemic onse t JIA \200 Etiology and pathophysiology Unknown. At the outset the systemic features of fever and rash mimic infection, but no infectious agent can be found. There is only limited evidence for a genetic link in the disease. Anemia (usually of chronic in \202 ammation, may also be GI blood loss secondary to medica tion). Leukocytosis with neutrophilia. Thrombocytosis. ESR often >100 mm/h. CRP elevated. F ibrinogen, immunoglobulins, and complement C3 and C4 raised. Autoantibodies including ANA, ANCA negative. Ferritin is high [if very high consider macrophage activation syndrome (MAS) ]. LDH low/normal. If raised consider malignancy. Imaging \200\223 US of joints helpful if synovitis present. Radiographs usually normal at baseline. Transthoracic echocardiogram fo r pericarditis/ myocarditis and effusion. \200 \200 \200 \200 Clinical features Daily high spiking fevers are the most important criterion for diagnosis. Almost always fevers are present at the out- set of the illness. \200 The fever pattern is a single high spike in the afternoon or evening, falling to baseline o r below. Double temperature spikes are also seen. This typical quotidian (or double quotidi an) pattern may only become obvious once treatment with NSAIDs is started. The rash is pres ent in more than 90% of cases at the outset. It is a non- \201 xed erythematous rash, evan escent with fever and appearing as salmon-pink macules 2 \200\22310 mm in size that may coa lesce. The Koebner phenomenon is exhibited and it can resem- ble urticaria with mild prurit is. The liver is mildly enlarged and 30% of children have mild splenomegaly. There is gener alized lymphadenopathy in 50% with small, freely mobile, painless nodes. Serositis \200 \223 typically pericarditis with or without effusion is usually mild and asymptomatic. Myoc arditis occurs infrequently and there is rarely car- diac compromise. Pleuritis and periton itis can occur. Arthritis is only present at onset of the disease in about a third of patie nts (symmetrical and polyarticular). Arthritis will often develop within the \201 rst few months if not at the outset. Knees, wrists, ankles, and C-spine are commonly involved. \200 \200 Differential diagnosis Many children present systemically unwell with fevers and rash. The primary differential diagnosis then includes infec- tious disease and malignancy. \200 There are no pathognomonic laboratory test results for systemic onset JIA. Investigations a re aimed at ruling out other diagnoses. If leukemia remains a possibility, a bone marrow as pira- tion/biopsy must be performed. Kawasaki disease (fever, rash, joint pains) must be co nsid- ered in younger children, as well as other vasculitides and fever syndromes (see p. 3 44). \200 Treatment Treat with NSAIDs initially. \200 Clinical complications Macrophage activation syndrome Alternatively described as secondary haemophagocytic lymphohistiocytosis. Characterized by: \200 Ibuprofen at 60 mg/kg/day (6 divided doses), indomet- acin at 1 \200\2232 mg/kg/day (2 divi ded doses). Glucocorticoids (GCs) are used for systemic symptoms (e.g. intravenous methylpr ednisolone 30 mg/kg/day for three consecutive days, repeated as required). Fever, hepatosplenomegaly, bruising and coagulopathy, encephalopathy (dizzy, lethargy, diso rientation). CHAPTER 10 Juvenile idiopathic arthritis 363 Resources See after section Juvenile idiopathic arthritis: overview Pulse methylprednisolone may result in lower cumula- tive doses of GCs over time compared w ith high dose oral prednisolone. Oral prednisolone can be given at doses of 1 \200\2232 mg/ kg/ day in 2 \200\2233 divided doses initially. Disease modifying anti-rheumatic drugs (DMA RDs) should be started early. Subcutaneous methotrexate is the usual first line DMARD. Cycl ophosphamide and ciclosporin can be used for severe cases or where methotrexate has failed or chil- dren are intolerant of it. Anakinra, a recombinant IL-1 receptor antagonist, is un der study and preliminary reports suggest 79% of sys- temic onset JIA patients responding ( Verbsky, 2004). Anti IL-6 antibody (MRA) is theoretically bene \201 cial and requires furt her study. References Lomater C, Gerloni V, Gattinara M, Mazzotti J, Cimaz R, Fantini F. Systemic onse t juvenile rheumatoid arthritis; A retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol 2000; 27: 491 \200\2236. Still GE. On a form of chronic joint disease in children. Med Chir Trans 1897; 80: 47. Verbsky JW. White AJ. Effective use of the recombinant interleukin- 1 receptor agonist anak inra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 2004; 3 1: 2071 \200\2235. See also Juvenile idiopathic arthritis: overview Kawasaki disease Natural history and prognosis Three disease courses are described: \200 \200 Monocyclic: remits completely (11%). Polycyclic: relapses with intervals of remission some lasting several years (34%). Unremitting: about 55% who never go into remission and suffer long-term disability. JUVENILE PSA 364 Juvenile PsA Psoriatic arthritis in children has only recently been recog- nized as a distinct condition within the JIA spectrum. Juvenile PsA (JPsA), as in adults, may pre-date psoriasis by many years (may be 15 years or more) and for this reason the condition has been under-diagnosed . Examination of the nails for pitting, splitting of the free edge, salmon pink subungual dis colouration, and subun- gual hyperkeratosis. Asymptomatic uveitis occurs in up to 20% of ch ildren with JPsA in a pattern similar to that seen in oligo-JIA. Screening is therefore imp ortant. Classi \201 cation See the ILAR classi \201 cation; see Juvenile idiopathic arthritis: ov erview (see p. 352). Investigations As with other forms of JIA. Speci \201 c scanning protocols and appearances of JPsA-related dactylitis using MR and US are not well developed. Note: male >6 yrs and HLA-B27 +ve are excluded, as are those with enthesitis, sacroiliitis, or a spondyloarthropathy. Treatment The management of JPsA is similar to the management ad- opted for oligo-JIA or po lyarticular JIA, and is dependant on the extent of joint involvement. Since the prognosis i s worse for JPsA than it is for oligo-JIA, immunosuppression is usually started early in th e disease course. Methotrexate is the \201 rst-line choice. Epidemiology Prevalence \201 gures are dif \201 cult to estimate because of changes to t he classi \201 cation of the condition. \200 The annual incidence of JPsA is in the order of 0.23 \200\2230.4 per 100 000 children. JPsA represents 2 \200\22315% of all children with JIA (Symmons, 1996). There is a female prepo nderance of 2:1 and mean age of onset is 6 years old (but children as young as 1 year old m ay be affected). Prognosis The ILAR classi \201 cation differs from previous classi \201 cation systems an d, therefore, there are few data on long-term follow-up and prognosis in this condition. Fr om one case series, about 40% of JPsA children have persisting active disease, progressing to a polyarthritis, at 7-year follow-up, and 8% were severely functionally limited (Roberto n, 1996). Clinical features Asymmetric arthritis of both large and small joints is char- acteristic o f JPsA. \200 \200 Sacroiliitis occurs in a very small minority. In many ways, the presentation is similar to oligo-JIA with onset in early childhood, female preponderance and the occurrence of asympto matic chronic uveitis. Unlike in oligo-JIA dactylitis is frequent, and both small and large joints are involved. Dactylitis represents the combination of arthritis and tenosynovitis, and the clinical picture is one of swelling extending well beyond the margins of any joint capsule. JPsA dactylitis is usually asymmetrical and frequently involves the second toe. I n 33 \200\22367% of children arthritis predates psoriasis. Careful examination of the hairl ine, behind the ears, the naval, groin, and natal cleft should be undertaken. References Roberton DM, Cabral DA, Malleson P, Petty RE. Juvenile psoriatic arthritis: Foll owup and evaluation of diagnostic criteria. J Rheumatol 1996; 23:166 \200\22370. Symmons DP, Jones M, Osborne J, et al. Pediatric rheumatology in the United Kingdom: data f rom the British Pediatric Rheumatology Group National Diagnostic Register. J Rheumatol 1996 ; 23: 1975 \200\22380. 365 Chapter 11 Pregnancy and the rheumatic diseases Pregnancy and the rheumatic diseases 366 PREGNANCY AND THE RHEUMATIC DISEASES H. HARRY 366 Pregnancy and the rheumatic diseases Most rheumatic diseases are associated with normal fertility. However some diseases, such a s lupus, are asso- ciated with autoimmune ovarian failure. Additionally, severe disease may require treatment with regimes including high dose glucocorticoids or cyclophosphos- phami de therapy, which may reduce fertility. Most rheumatic diseases that are well controlled pr ior to conception do not deteriorate in pregnancy, provid- ing that the patient continues w ith appropriate disease- modifying therapy. Some patients with in \202 ammatory disease ex perience disease remission during pregnancy. Postpartum flare is common in all the rheumati c diseases. Poor disease control at conception is the best predictor of disease \202 ares in pregnanc y, while conversely, good control re \202 ects a lower risk of \202 ares. Complications of lupus \200 Hypertension: a fourth of lupus pregnancies are asso- ciated with hypertension. Hypertensio n is associated with renal disease and glucocorticoid use, and results in an increased risk of intrauterine growth restriction, and a higher rate of Cesarean section. Lupus nephritis : renal disease is associated with a poor fetal outcome and increased risk of maternal comp lica- tions. Active renal disease is a contraindication to preg- nancy. Improved disease co ntrol is mandatory before embarking on pregnancy, and disease remission is rec- ommended fo r at least 6 months prior to conception. Differentiating between pre-eclampsia and lupus ne phri- tis with onset during pregnancy may be challenging, but autoantibodies, evidence of c omplement consumption and clinical evidence of disease activity may be useful in assessment . Complement levels rise in normal preg- nancy and in pre-eclampsia. A positive urinary sed iment with cell or casts makes lupus nephritis more likely than pre-eclampsia. HELLP (haemo lysis, elevated liver enzymes, low platelets) makes pre-eclampsia more likely but these fea tures may also be features of active lupus. Pre-eclampsia may be exacerbated by glucocortic oid therapy, but is the acute treatment of choice in patients with lupus nephritis. Pulmona ry hypertension in lupus is rare, but has an associated mortality of 50% in pregnancy. Rheumatoid arthritis Effect of pregnancy on disease \200 Signi \201 cant improvement in disease activity is reported in 75 \200\22395% of pregnant women with RA, with full remission reported in only 16% in one series. The improvement star ts in the first trimester and continues throughout pregnancy, with most women reporting the best disease control in the last trimester. In up to a fourth of pregnancies, there is no improve- ment or deterioration in symptoms. Flares in the postpartum period are common. It is unclear why the majority of women improve in pregnancy and, although immunoregulation, c ytokine expression, HLA antigens, microchimerism and innate immunity have all been postulat ed to play a role, the exact mechanism remains elusive. Pregnancy does not appear to impact on the long-term outcome of joint damage. New onset RA is 3 \200\2235 \227 more common in the postpartum period. \200 Effect of disease on pregnancy \200 Lupus is not known to affect fertility. However, there is an association with increased fet al and maternal complications in patients undergoing fertility treatments such as IVF. Prem ature delivery is common in patients with lupus, and occurs in up to 55%. Fetal outcome (IU GR, prema- turity, and fetal loss) in women with lupus nephritis is better in women with no rmal renal function, well- controlled blood pressure, and no signi \201 cant proteinuria a t conception. Effect of disease on pregnancy \200 Patients with rheumatoid arthritis do not have reduced fertility. However, high disease act ivity may result in menstrual cycle disturbance or anovulatory cycles due to high dose gluc ocorticoid therapy. It remains unclear if RA is associated with an increased risk of miscar riage/spontaneous abortion. Pre-eclampsia is more common in patients with RA. Effect of disease on the fetus \200 Pregnancies in SLE patients are associated with a greater risk of stillbirth, abortion, and premature delivery than in the general population. The risk is increased in women who have previously experienced fetal loss, have active renal disease at con- ception, maternal hyp ertension, and the presence of antiphospholipid antibodies. The prevalence of Ro and La ant ibodies in SLE patient is 35%, but transmission of IgG antibodies across the placenta occur s in about 5% of mothers between weeks 16 and 32 gestation, and may result in neonatal lupu s from week 16. Presentation includes cutaneous lupus, complete heart block, cytopaenia, he patic and other manifestations. Resolution typically occurs within the \201 rst 6 months of life. Effect of disease on the fetus There is no association between poor fetal outcome and sever ity of RA, although prematurity and low birth weight have been reported in patients with RA . SLE Effect of pregnancy on disease \200 It remains unclear if pregnancy results in an increased risk of flares in women with lupus as the data are con \202 icting. Increased frequency of \202 ares may re \202 ect withd rawal of therapy during pregnancy. Flares can occur during pregnancy or in the immediate po stpartum period, and are usually mild and respond to low dose glucocorticoids, hydroxychlor oquine, and or azathioprine CHAPTER 11 Pregnancy and the rheumatic diseases 367 Complete congenital heart block (CHB) is diagnosed when fetal bradycardia is detected betwe en 18 and 28 weeks. Monitoring involves serial Doppler echocardiography. Incomplete congeni tal heart block may progress in utero or post-delivery, and carries a 20% mortality rate. P ermanent pacemakers are required by 67% of complete CHB survivors. Dexamethasone may revers e \201 rst and second degree heart block, but is ineffective in complete heart block. Hal f the cases of neonatal lupus will occur in pregnancies where the woman has not been diagno sed with a con- nective tissue disease, but who often develop Sj gren s syndrome or lupus in the next 10 years. The risk of intrauterine growth restriction is increased in pregnanci es in women with SLE, particularly those with hypertension, active lupus, and co-existing A PLS as signi \201 cant predictive factors. thrombocytopenia is recognized to occur due to the transmission of anti-platelet antibodies across the pla- centa. Thrombotic complications in the neonate are rare. Intrauterine grow th restriction of the fetus is more common in women with APLS. Premature delivery is common in patients with APLS. Sjogren \200\231s syndrome Effect of disease on pregnancy \200 Sjogren \200\231s syndrome normally presents in older women, although normal fertility is r eported in those women of childbearing age. If disease is well controlled and stable at con ception, the outcome of pregnancy is generally favorable, as long as treatment with mainten ance therapy is continued during pregnancy. Systemic sclerosis Effect of pregnancy on disease \200 Antiphospholipid syndrome Effect of disease on pregnancy \200 Systemic sclerosis does not usually progress during preg- nancy, but pulmonary hypertension should be excluded as a cause of breathlessness in women in later pregnancy, a commonly re ported symptom in normal advanced pregnancy. Women with pre-existing pulmonary hypertension should be discouraged from pregnancy due to the high mortality of around 50%, which is see n in women with any cause of pulmonary hypertension. Symptoms of Raynaud \200\231s phenomen on and skin involve- ment may improve in pregnancy, although skin disease may deteriorate p ostpartum. Hypertensive renal crises are commoner in women with a diagnosis of systemic scl erosis made in the last 5 years, and can mimic pre-eclampsia or eclampsia. ACE inhibi- tors offer protection against renal crises and are used in pregnancy despite the risk of fetal malformation, and only after counseling. Renal crises in a previous pregnancy does not excl ude a further pregnancy, but hypertensive control is vital prior to conception. It remains unclear whether APLS is associated with infer- tility. In those undergoing ferti lity treatment, there is an increased risk of thrombosis during ovarian induction as well a s later in pregnancy. Normal pregnancy results in an increased thrombotic tendency from con ception to 6 weeks following delivery. APLS further increases the risk of arterial and veno us thrombosis, but a better fetal outcome is reported in women taking low dose aspirin who have had an early miscarriage. Pre-eclampsia results in multiple placental infarcts and pla cental insuf \201 ciency. In APLS pre-eclampsia may occur early and before 20 weeks. Altho ugh supportive treat- ment is indicated initially, delivery of the fetus is the de \201 ni tive treatment in both cases. HELLP is also commoner in patients with APLS. Effect of disease on the fetus \200 Recurrent fetal loss is also one of the criteria when diagnosing APLS, and the presence of both lupus antico- agulant and anticardiolipin antibodies is associated with the highest ri sk of fetal loss. Fetal loss in early pregnancy in women with APLS can be due to failure of the placenta to implant, the effect of antiphospholipid antibodies on anionic phospholipid s or the effect of B2-glycoprotein on trophoblasts. Thrombosis in APLS is also thought to h ave a role in pregnancy loss due to uteroplacental insuf \201 ciency from multiple placent al thromboses and infarcts. The use of aspirin and heparin in pregnancy probably reduces mi scarriages by an antithrombotic mechanism, as well as by preventing pathological apoptosis and anti-complement effects. Anticoagulation with heparin, rather than low dose aspirin is indicated in women with recurrent miscarriages, thromboembolic events or stillbirth. A good predictor of adverse pregnancy outcome is Doppler ultrasound examination during the second trimester and an abnormal uterine artery wave form is one predictor of fetal or neonatal d eath. Non-autoimmune causes of thrombocytopenia include normal pregnancy, where thrombocyto penia is mild and affects 9%. However, in mothers with APLS, neonatal Effect of disease on pregnancy \200 Normal fertility has been reported in women with systemic sclerosis. Premature delivery is common in patients with systemic sclerosis. Spondyloarthropathy The effect of pregnancy on disease \200 The majority of cases improve in pregnancy, especially those with small joint involvement. A fourth of patients with primarily spinal involvement experience a \202 are of their sym ptoms. Uveitis often improves during pregnancy. Effect of disease on pregnancy \200 The spondyloarthropathies are not known to directly impair fertility. Postpartum \202 are s are common. Vasculitides Effect of pregnancy on disease \200 Women of childbearing age are rarely affected by the vasculitides, so there is little data for pregnancy in women with vasculitis. PREGNANCY AND THE RHEUMATIC DISEASES H. HARRY 368 In all of the vasculitides, disease control should be maxi- mal prior to conception due to poor fetal outcomes and maternal mortality. Pre-eclampsia and renal vasculitis need to be d ifferentiated from each other. hydroxychloroquine is excreted in breast milk, there appear to be no long-term sequelae in infants. Methotrexate Methotrexate crosses the placenta and high dose in preg- nancy is associated w ith a speci \201 c pattern of fetal abnor- malities, involving the cranium, central nervou s system, and limbs. The risk in women prescribed low dose methotrex- ate, however, is less clear, and although a higher risk of spontaneous abortion has been reported than in contro ls (20%), the data are con \202 icting with regard to congenital abnormalities. As a conse quence of this, current recom- mendations are that methotrexate is stopped 3 \200\2234 mont hs prior to conception. Methotrexate is also contraindicated in women who are breastfeeding as methotrexate is excreted into breast milk. Effect of disease on pregnancy \200 \200 The vasculitides are not known to directly affect fertility. Premature delivery is common i n patients with vasculitis. Takayasu \200\231s arteritis \200 Takayasu \200\231s in pregnancy may be complicated by pre- eclampsia, antepartum hemorrhage , stroke (thrombosis and bleed), and sepsis. Renal involvement may be dif \201 cult to dif ferentiate from pre-eclampsia. Sulphasalazine Both sulfasalazine and its metabolite sulfapyridone cross the placenta. Alth ough there are reports of an increase in oral cleft, cardiac, renal, and neural tube defect s, the main bulk of the evidence does not support this, and the risk of teratogenicity is l ow. Sulfasalazine is also present in breast milk and caution is therefore advised in women who breastfeed. Be het \200\231s vasculitis. Women with Be het \200\231s disease carry an increased risk of thrombosis due to both the disease and pregnancy itself. Central venous thrombosis may o ccur and should be treated with heparin. Wegener \200\231s granulomatosis \200 Wegener s granulomatosis may present during preg- nancy. In those with established disease, the commonest time for \202 ares is in the \201 rst or second trimester, or post- part um. Glucocorticoids and azathioprine have been used successfully in pregnancy. Cyclophospha mide is more toxic and is rarely recom- mended in pregnancy, but has been used successfully in the third trimester. Le \202 unomide Le \202 unomide has been shown to be teratogenic in animals, although exp osure in early pregnancy in humans has not been reported to result in abnormalities. Howeve r, be- cause of the potential to cause severe fetal abnormalities, the drug should be disco ntinued, and women either wait 2 years for elimination of the drug, or undergo cholestyr- a mine chelation and wait for a further 3 months before embarking on a pregnancy. Drug levels should be checked in this instance. Le \202 unomide should also be avoided in breast feed ing mothers. Churg \200\223Strauss vasculitis Churg \200\223Strauss vasculitis is associated with flares in pregnancy and during the postpartum period. Drug treatment in patients with rheumatic disease in pregnancy In every individual case, th e risk/bene \201 t ratio of exposure to drugs and the risk of disease \202 are should be undertaken. Azathioprine There is a well established good safety pro \201 le in pregnancy. Immunosuppr ession in infants has been reported. Ciclosporin There is an association with intrauterine growth restriction, although whether this relates to drug treatment or maternal disease is unclear. Non-steroidal anti-in \202 ammatory drugs NSAIDs cross the placenta and are associated wit h relative safety in early pregnancy, although there have been report of oral cleft, cardia c, and gastric defects along with an increased risk of miscarriage. In late pregnancy, ther e is a well established association with premature closure of the ductus arteriosis. Impair ed renal development, oligohy- dramnios, and fetal hemorrhage have been reported in late pr egnancy, and NSAIDs should therefore be avoided from 32 weeks of pregnancy. There is a spar city of data for COX-11 inhibitors and these agents should therefore be avoided in pregnanc y. Mycophenolate mofetil Digital and corpus callosum abnormalities are recognized fetal abnorm alities in pregnancies exposed to mycophe- nolate mofetil, and therefore this drug should b e avoided. Anti-tumor necrosis factor agents Although patients are counseled not to become pregnant wh ilst being treated with anti-TNF therapies, there have been successful pregnancies when eit her parent has been treated with anti-TNF therapy. It remains unclear if anti- TNF therapie s cross the placenta or into breast milk, and the effect this may have on the fetus. Althou gh the total number of pregnancies exposed to anti-TNF therapy is low, the incidence of abn ormalities appears no higher than that expected in the general population. Glucocorticoids Glucocorticoids are considered to be safe in pregnancy. Prednisolone is mai nly metabolized, so very little crosses the placenta in doses up to 20 mg daily. However, h igh doses of glucocorticoids are associated with an increased risk of pre-eclampsia, pregna ncy \210\222induced hypertension, gestational diabetes, infection, and premature rupture of membranes Anakinra There are no data to support safety or raise safety issues in pregnancy or lactati on in either animals or humans. Hydroxychloroquine Hydroxychloroquine crosses the placenta, raising a theo- retical possibi lity of fetal toxicity. However, there appears to be no increased risk of fetal malformatio n in a number of small observational longitudinal studies. Even though Rituximab There are no data in pregnancy or lactation, and pregnancy should therefore be av oided. CHAPTER 11 Pregnancy and the rheumatic diseases 369 Abatacept There are no data in pregnant humans, although in animal studies no increased ter atogenicity is reported. Pregnancy should be avoided in pregnancy. Ankylosing spondylitis and pregnancy. Available at: http:// www.asresearch.co.uk/pregnancy. htm and http:// www.nass.co.uk/life.htm Systemic sclerosis and pregnancy. Available at: htt p:// www.patient.co.uk/showdoc/40002313/ Cyclophosphamide Cyclophosphamide therapy is contraindicated in the \201 rst and second t rimesters of pregnancy, but has been used successfully in the third trimester in severe dis ease. Therapy is associated with premature, irreversible, ovarian failure, but is less like ly in women under the age of 26, and those with a lower cumulative dose. Premature ovarian failure due to cyclophosphamide therapy is reported as between 11 and 59%. Although there h as been interest in preserving fertility in this subgroup, there are no data to support the use of the combined oral contraceptive pill, although gonadotrophin- releasing hormone may be promising in this situation. ICD-10 codes O00 to O99 See also Chapter 19 p. 531 Drug therapies Chapter 8 p. 240 SLE, antiphospholipid syndrome References Barrett JH, Brennan P, Fiddler M, Silman AJ. Does rheumatoid arthritis remit dur ing pregnancy and relapse postpartum? Results from a nationwide study in the United Kingdom performed prospectively from late pregnancy. Arthritis Rheum 1999: 42: 1219 \200\22327. Boumpas DT, Austin HAIII, Vaughan EM, Yarboro CH, Klippel JH, Balow JE, Risk for sustained amenhorrhoea in patients with systemic lupus erythematosis receiving intermittent pulse cyc lophosphamie therapy. Ann Intern Med 1993; 119: 366 \200\2239. Role of multidisciplinary team Physiotherapy input in pregnant patients is important for ad vice about maintaining muscle strength and stability around joints where ligaments are subj ected the hormonal in \202 uences resulting in increased joint laxity. Occupational therap ists may have signi \201 cant input into self-management for the mother and care of the ch ild. Review of maternal needs may cover appropriate splinting, and household and work needs both during pregnancy and postpartum. Func- tional problem areas, which may be covered inc lude modi \201 - cation of suitable baby equipment, and childcare techniques, for example, when feeding and or carrying the infant. Brucato A, Doria A, Frassi M, et al. Pregnancy outcome in 100 women with autoimmune disease s and anti-Ro/SSA antibodies: a prospective controlled study. Lupus 2002; 11: 716 \200\2232 1. Buyon JP, Clancy RM. Neonatal lupus syndromes. Curr Opin Rheumatol 2003; 15: 535 \200\22341. Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy a randomized, c ontrolled trial of treatment. Obstet Gynecol 2002; 100: 408 \200\2231342: 1219 \200\22327. Gayed M, Gordon C. Pregnancy and rheumatic diseases. Rheumatology 2007; 46: 1634 \200\22340. Tools The lupus activity index in pregnancy (LAI-P) has been validated and a version of BIL AG-2004 for use in pregnancy is currently being developed. Golding A, Haque UJ, Gile JT. Rheumatoid arthritis and reproduction. Rheum Dis Clin N Am 2007; 33: 319 \200\22343. Gordon C. Pregnancy and autoimmune diseases. Best Pract Res Clin Rheumatol 2004; 18: 359 \200\22379. Iijima T, Tada H, Hidaka Y, et al. Prediction of postpartum onset of Patient advice Counseling patients about the need for improved disease control prior to con ception, potential complications to both mother and fetus, and the risk of \202 ares in t he post- partum period should be discussed. Screening for compli- cations should be underta ken regularly during pregnancy, and the risks and bene \201 ts of drug therapies, both in preg- nancy and whilst breastfeeding, discussed. rheumatoid arthritis. Ann Rheum Dis 1998; 57: 460 \200\2233. Kong NC. Pregnancy of a lupus patients \200\223 a challenge to the nephrologist. Nephrol Dial Transplant 2006; 21: 268 \200\22372. Mok CC, Wong RW. Pregnancy in systemic lupus erythematosus. Postgrad Med J 2001; 77: 157 \200\22365. Ostensen M, Forger F, Nelson JL, Schuhmacher A, Hebisch G, Villiger PM. Pregnancy in patien ts with rheumatic disease: anti- in \202 ammatory cytokines increase in pregnancy and decr ease post partum. Ann Rheum Dis 2005; 64: 839 \200\22344. Ostensen M, Villiger PM. The remission of rheumatoid arthritis dur- Monitoring in pregnancy Monitoring of both mother and fetus should be under- taken regularl y. In the mother, disease activity and disease complications such as renal involvement shou ld be sought. Additionally, close monitoring for complications of preg- nancy, such as thro mbo-embolic disease and pre-eclampsia, particularly in those patients with SLE, APLS, vascu litis, and systemic sclerosis, should be undertaken. In the fetus, close monitoring to dete ct IUGR, fetal abnormalities and abnormalities in uterine blood \202 ow waveform should b e regularly performed. ing pregnancy. Semin Immunopathol 2007; 29: 185 \200\22391. Petri M, Allbritton J. Fetal outcome of lupus pregnancy: a retrospec- tive case-control stu dy of the Hopkins Lupus Cohort. J Rheumatol 1993; 20: 650 \200\2236. Ruiz-Irastorza G, Khamashta MA, Gordon C, et al. Measuring systemic lupus erythematosis act ivity during pregnancy: valida- tion of the lupus activity index in pregnancy scale. Arthri tis Rheum 2004; 51: 78 \200\22382. Yee CS, Farewll V, Isenberg DA, et al. Revised British Isles Lupus Assessment Group 2004 In dex: a reliable tool for assessment of systemic lupus erythematosis activity. Arthritis Rhe um 2006; 54: 3300 \200\2235. Resources Internet sites Systemic lupus erythematosis and pregnancy. Available at: http://w ww.uklupus.co.uk/fact13.html and http:// www.uklupus.co.uk/preg.html Rheumatoid arthritis a nd pregnancy. Available at: http:// www.rheumatoid.org.uk/article.php?article_ id=83 and ht tp://www.arc.org.uk/arthinfo/ patpubs/6060/6060.asp This page intentionally left blank 371 Chapter 12 Osteoarthritis and related disorders Osteoarthritis 372 Osteoarthritis-related disorders 380 OSTEOARTHRITIS 372 Osteoarthritis Osteoarthritis (OA) is a mechanically driven, but biochemically-mediated disease of synovia l joints. The ACR classi \201 cation criteria for OA Hand OA Pain, aching or stiffness in the handa and 3 of the following: \200 Bony swelling of \211 2 distal interphalangeal (DIP) joints . Bony swelling of 2 or more of 10 selected joints*. <3 swollen metacarpophalangeal (MCP) j oints. Deformity of 2 or more of 10 selected joints*. De \201 nition In clinical practice, as in epidemiologic studies, OA is diag- nosed where there is joint pain, together with characteris- tic radiographic changes, in the absence of an alternative cause. Surprisingly, one of the most useful de \201 nitions of OA is to be found on Wikipedia: \200 \200 \200 Osteoarthritis (OA, also known as degenerative arthritis or degenerative joint disea se, and sometimes referred to as \200\230arthrosis \200\231 or \200\230osteoarthrosis \200\231), is a condition in which low-grade in \202 ammation results in pain in the joint s, caused by wearing of the cartilage that covers and acts as a cushion inside joints. As t he bone surfaces become less well protected by carti- lage, the patient experiences pain up on weight bear- ing, including walking and standing. Due to decreased movement because of t he pain, regional muscles may atrophy and ligaments may become more lax. OA is the most com mon form of arthritis. The word is derived from the Greek word \200\230osteo \200\231 mean ing \200\230of the bone \200\231, \200\230arthro \200\231 meaning \200\230joint \200\231 , and \200\230itis \200\231 meaning in \202 ammation, although many sufferers have little or no in \202 ammation \200 Knee OA: using history and examination Pain in the kneea and 3 of the following: \200 \200 \200 \200 \200 \200 Age >50 years. Morning stiffness <30 min. Crepitus on active motion. Bony tenderness. Bony enlargement. No palpable warmth of synovium. Hip OA: using history, examination and laboratory \201 ndings Pain in the hipa and: \200 Internal rotation \211 15 and either ESR \211 45 mm/h or hip \202 exion \211 115 i f ESR unavailable. Or \200 A more unwieldy, but widely quoted de \201 nition is from the American Academy of Orthoped ic Surgeons (1995): Internal rotation >15 with pain, morning stiffness \211 60 minutes, >50 years old. \200 Osteoarthritis diseases are a result of both mechanical and biologic events that des tabilize the normal coupling of degradation and synthesis of articular cartilage chondrocyt es, extracellular matrix and subchondral bone. Although they may be initi- ated by multiple factors such as genetic developmen- tal, metabolic, and traumatic factors, osteoarthritis diseases are manifest by morphologic, biochemical, molecular and biomechanical changes of b oth cells and matrix which leads to a softening, \201 brillation, ulceration and loss of articular cartilage, sclerosis and eburnation of subchondral bone, osteophytes and subchond ral cysts. When clinically evident, osteoar- thritis diseases are characterized by joint pa in, tenderness, limitation of movement and variable degrees of in \202 ammation without sy stemic effects. aOn most days of the previous month. bRight and left 2nd and 3rd proximal interphalangeal j oints, 2nd and 3rd DIPJ, and 1st carpometacarpal joints. Patterns of OA Primary \200 \200 \200 \200 Nodal (hand). Erosive (hand). Generalized (hand + knee/hip). Diffuse idiopathic skeletal hy perostosis (DISH). Secondary \200 \200 \200 \200 \200 Localized (e.g. fracture, infection). Diffuse (e.g. secondary to rheumatoid arthritis). Cal cium pyrophosphate dihydrate (CPPDD) deposition. Metabolic (e.g. haemochromatosis; ochronos is). Neuropathic [e.g. tabes dorsalis, diabetes mellitus (DM)]. Bone dysplasias. Classi \201 cation The American College of Rheumatology (ACR) criteria were developed to d ifferentiate OA from other, especially in \202 ammatory, arthritides in specialist practic e. Epidemio- logical studies usually classify occurrence of OA on the basis of radiographic changes alone. However, the presence of pain in addition to osteophytes or joint space nar rowing is now generally accepted. Epidemiology OA is the commonest arthropathy, typically affecting joints most exposed to me chanical load, including the hand, knee, hip, and 1st MTP joints. \200 Spondylosis The term given to the (degenerative) process causing reduced intervertebral dis c space. Synovial facet joints are typically secondarily affected by an OA process; however , primary OA of facet joints can occur. The degree to which costovertebral and costotransve rse joints are affected by OA is not well documented. The prevalence of radiographic changes alone in anyone >50 years old is notable: hip 8%; ha nd 15%; knee 30%. About 50% of these people will have pain over a 1-year period. Robust UK incidence data is lacking. Incidence data from the United States of America shows an age- a nd sex-standardized incidence for symptomatic knee OA of CHAPTER 12 Osteoarthritis and related disorders 373