44 Annals ofthe Rheumatic Diseases 1993; 52: 44 48 Musculoskeletal manifestations in hyperlipidaemia: Ann Rheum Dis: first published as 10.1136/ard.52.1.44 on 1 January 1993. Downloaded from a controlled study P Klemp, Anne M Halland, F L Majoos, Krisela Steyn Abstract arthritis, and oligoarthritis. '-' The reported Eighty eight patients with hyperlipidaemia (81 prevalence of these manifestations varies widely white patients from South Africa and seven from study to study because of differences in patients of mixed race from the West Cape classification of the hyperlipidaemias, patient area) were studied. Forty eight had adult selection, and study design. Interpretation of familialhypercholesterolaemia, 16had juvenile the findings, none of which included control familial hypercholesterolaemia, and 24 had patients, is difficult especially where prevalence mixed hyperlipidaemia (increased cholesterol figures are low. Migratory polyarthritis appears and triglycerides). They were interviewed and to be particularly associated with homozygous examined and their musculoskeletal mani- familial hypercholesterolaemia.' There are, festations compared with 88 controls with however, other uncontrolled studies which normal lipid profiles, and matched for age, show no specific associations between hyper- sex, and race for each group of patients. The lipidaemia and rheumatic disorders.' '1 foliowing manifestations were significantly In the one controlled study the only difference increased inthepatients: (a) tendon xanthomas between patients with hypercholesterolaemia particularly of the tendo Achiflis in patients and controls was that pain, particularly of the with adult familial hypercholesterolaemia and ankles and feet, was significantly more severe in mixed hyperlipidaemia; (b) tendo Achillis the patients." There was no difference in the tendinitis in patients with adult familial hyper- duration of morning stiffness, analgesic use, or cholesterolaemia and mixed hyperlipidaemia; effect on lifestyle. This study cannot be com- and (c) oligoarthritis in patients with mixed pared with others, however, as specific entities hyperlipidaemia but not in those with adult such as xanthomas and migratory polyarthritis familial hypercholesterolaemia. Migratory were not reported. polyarthritis and transient tendo Achillis pain We documented the musculoskeletal system were rare. Thirty eight per cent of patients manifestations of 88 patients with hyper- with juvenile familial hypercholesterolaemia lipidaemia and compared them with 88 age and http://ard.bmj.com/ had musculoskeletal system manifestations sex matched controls. The patients were sub- none of which was significantly increased divided into groups with different lipid profiles. compared with controls. There was a signi- The onset of the manifestations in relation to ficant association between tendon xanthomas the diagnosis of hyperlipidaemia and the effect and tendo Achillis tendinitis. There was a oflipid lowering treatment on the manifestations in pretreatment chole- were also investigated. significant difference on October 2, 2021 by guest. Protected copyright. sterol levels in the patients with adult familial hypercholesterolaemia and musculoskeletal system manifestations compared with those Patients and methods without and in ali three groups combined. The Eighty eight consecutive patients with hyper- study confmms an association between hyper- lipidaemia attending the lipid clinic at Tygerberg lipidaemia and tendon xanthomas, tendo Hospital were studied. They were interviewed Achillis tendinitis, and to a lesser extent with a detailed questionnaire and examined, oligoarthritis but not migratory polyarthritis and the following information was recorded: Rheumatology Unit, or tendo Achillis as in age, sex, family history of hyperlipidaemia or Department of transient pain reported Internal Medicine, other studies. It also shows that musculo- ischaemic heart disease, musculoskeletal system University of skeletal system manifestations antedated the manifestations past or present, cholesterol and Stellenbosch Medical of in 24/39 triglyceride levels in patients with and without School, diagnosis hyperlipidaemia (62%) Tygerberg Hospital, patients and that the manifestations improved musculoskeletal system manifestations, the Cape Town, or resolved completely in 19/30 (63%) patients effect of lipid lowering treatment on musculo- South Africa after receiving lipid lowering treatment. It is skeletal system manifestations, and whether the P Klemp A M Halland therefore important to recognise the asso- onset of musculoskeletal system disorders F L Majoos ciation between musculoskeletal system antedated or followed the diagnosis of hyper- Lipid Clinic, manifestations and hyperlipidaemia for lipidaemia. Particular attention was paid to a Tygerberg Hospital, diagnostic and therapeutic reasons. history of migratory polyarthritis, oligoarthritis, 7505 Tygerberg, tendo Achillis tendinitis, and transient tendo South Africa K Steyn (Ann Rheum Dis 1993; 52: 414 48) Achillis pain. Correspondence to: P Klemp, A number of studies suggest that there is an Queen Elizabeth Hospital, association between hyperlipidaemia and CLASSIFICATION OF HYPERLIPIDAEMIA Rotorua, New Zealand. tendo Achillis Patients were classified as follows. (a) Hyper- Accepted for publication tendon xanthomas, tendinitis, 20 August 1992 transient tendo Achillis pain, migratory poly- cholesterolaemia without hypertriglyceridaemia Musculoskeletal manifestations in kvperlipidaemnia 45 in patients at least 16 years old if(i) pretreatment sterol less than the 50th centile for age'2 and total cholesterol was greater than or equal to 6-5 normal triglyceride levels (<2-0 mmol/l). The mmol/l, (ii) normal triglyceride levels (-2 0 normal range for cholesterol and triglyceride Ann Rheum Dis: first published as 10.1136/ard.52.1.44 on 1 January 1993. Downloaded from mmol/l), (iii) strong family history of ischaemic levels is the same in the two race groups. heart disease or familial hypercholesterolaemia. This group of patients was considered to have type Ila adult familial hypercholesterolaemia. LIPID ANALYSIS (b) Hypercholesterolaemia without hypertrigly- The plasma was stored at 4°C and analysed ceridaemia in patients younger than 16 years if within 24 hours. The total cholesterol and high (i) pretreatment total cholesterol was greater density lipoprotein cholesterol levels were than or equal to 6-5 mmol/l, and (ii) and (iii) as measured on a Gilford autoanalyser using the for adult familial hypercholesterolaemia. These Boehringer Mannheim CHOD-PAP enzymatic patients are referred to as having juvenile method. High density lipoprotein cholesterol familial hypercholesterolaemia. (c) Mixed was measured after precipitation of the apo- hyperlipidaemia if (i) total cholesterol was protein B containing lipoproteins with man- greater than or equal to 6 5 mmol/l, and (ii) ganese heparin. The non-fasting triglyceride triglyceride levels were greater than or equal to levels were determined by the Boehringer 2-0 mmol/l. A family history of hyperlipidaemia Mannheim enzymatic Peridochrom method. In or ischaemic heart disease was not considered in each instance the Gilford autoanalyser was this group. calibrated against Preciset Cholesterol. Control Of the 88 patients 81 were white South serum samples used were Precinorm L as an Africans and seven were patients of mixed race external control and a pooled plasma as an from the West Cape area. Forty eight patients internal control. had adult familial hypercholesterolaemia, aged 19-68 years (mean 41), of whom 30 (63%) were women; 16 had juvenile familial hyperchole- STATISTICS sterolaemia, aged 5-16 years (mean 11), with The x2 test was used to compare the groups equal sex distribution; and 24 had mixed unless less than five manifestations per group hyperlipidaemia, aged 19-69 years (mean 48), were present when Fisher's exact test was used. of whom 16 (67%) were men. For the three In determining the difference in cholesterol and groups the mean cholesterol levels were adult triglyceride levels in patients with musculo- familial hypercholesterolaemia 9172, juvenile skeletal system manifestations and those familial hypercholesterolaemia 7-81, and mixed without, logarithmic transformations were hyperlipidaemia 8'69 mmol/l, and the mean applied to remove positive skewness apparent in triglyceride levels were adult familial hyper- cholesterol and triglyceride levels. cholesterolaemia 1 07, juvenile familial hyper- cholesterolaemia 0-77, and mixed hyper- lipidaemia 4-32 mmol/l. Results http://ard.bmj.com/ ALL MUSCULOSKELETAL SYSTEM MANIFESTATIONS Overall 65 (74%) patients and 50 (57%) controls CONTROLS had one or more musculoskeletal system mani- The controls, interviewed and examined in the festations (p=0 026). The manifestations same way as the patients, were 88 normal included those which previous studies have volunteers matched for age in decades, sex, and shown to be associated with hyperlipidaemia race for each group of patients. They had and others such as osteoarthritis, rotator cuff on October 2, 2021 by guest. Protected copyright. normal fasting lipid profiles with total chole- syndrome, epicondylitis, and meniscal tears. Three patients aged 10-18 years and none of the controls were hypermobile (a score of 4 or more n= lc on Beighton's 9 point scale'3). None had features 80r- of the hypermobility syndrome. Gout was Patients 70 n - 32 present in four patients with mixed hyper- k- ZI Controls u~~~~~~~~~~~~~~~~~~~~~~~~~~~