Hypothalamus-pituitary-adrenocortical and -gonadal axis in RA / M. Cutolo Running title / G.EDITORIAL Bajocchi et al. Distal musculoskeletal manifestations in

C. Salvarani1, F. Cantini2, I. Olivieri3

1Service of , Arcispedale ABSTRACT characterized by inflammatory involve- S.Maria Nuova, Reggio Emilia; In polymyalgia rheumatica (PMR) the ment of the distal articular and tenosy- 2Rheumatologic Unit, II Division of marked and distinctive symptoms of novial structures. Medicine, Hospital of Prato, Prato; proximal aching and stiffness have tend- A non-erosive, self limited, asymmetric 3 Service of Rheumatology, S.Carlo ed to draw attention away from the distal peripheral (predominantly af- Hospital, Potenza; Italy. musculoskeletal manifestations which fecting the knee and wrist) was found in Please address correspondence and also occur in this syndrome. Peripheral 25% of the patients. These data were in reprint requsts to: Dr. Carlo Salvarani, manifestations are present in about half keeping with the results of previous stu- Servizio di Reumatologia, Arcispedale S. Maria Nuova, Viale Umberto I, No 50, of all cases of PMR and include joint dies which demonstrated the presence of 42100, Reggio Emilia, Italy. , diffuse swelling of the distal peripheral synovitis in a percentage of E-mail: [email protected] extremities with or without pitting PMR patients oscillating between 20- edema, and carpal tunnel 30% (7). The occurrence of peripheral Clin Exp Rheumatol 2000; 18 (Suppl. 20): syndrome. Awareness of these findings arthritis, particularly in both hands, may S51-S52. will help to facilitate the proper diagno- create some difficulties in the differen- © Copyright CLINICAL AND sis and institution of appropriate therapy tial diagnosis between PMR and elderly EXPERIMENTAL RHEUMATOLOGY 2000. for this disease. onset seronegative RA (EORA). Some patients with EORA present with a be- Key words: Polymyalgia rheumatica, The hallmark for the diagnosis of poly- nign symmetric synovitis characterized RS3PE syndrome, elderly onset rheumatica (PMR) is the proxi- by a prompt and complete response to seronegative rheumatoid arthritis. mal involvement characterized by mark- (CS) and a clinical course ed aching and morning stiffness in the similar to PMR (8). Healey noted pa- and pelvic girdles and in the tients who developed episodes of PMR (1-3). The prominence assigned to and EORA at different times during their these proximal symptoms has probably follow-up (9). These patients have a overshadowed the less well character- clinical condition quite different from ized and more variable distal musculo- "classic" RA that most closely resembles skeletal manifestations. However, Bruce PMR. in the first published description of PMR A recent study from the Mayo Clinic exa- in 1888, noted distal findings in 2 of his mined the musculoskeletal manifesta- 5 patients (4). Case I had symptoms "af- tions in a population-based cohort of pa- fecting his hands and feet as well as his tients with (GCA) fol- wrists and ankles". Case IV had sym- lowed over 42-year period (10). Six of ptoms that laid "hold of his arms, shoul- 128 GCA patients identified during the ders, and hands which swelled and stiff- study period satisfied the criteria for RA. ened, and lost so much strength that he Four of them were seronegative for rheu- could not put his hand to his mouth and matoid factor and never developed joint had to be fed at meals like a child". erosions or extra-articular features of RA Successively, Bengt Hamrin accurately during their follow-up over a number of described in 1972 the presence of distal years. They experienced multiple se- extremity swelling with pitting edema in parate episodes of symmetrical arthritis, 25/93 (27%) PMR patients (5). proximal symptoms of PMR, and distal Despite these descriptions, distal symp- extremity swelling with pitting edema. toms have been underestimated and of- All of these manifestations responded ten a diagnosis of rheumatoid arthritis rapidly to CS without any disease pro- (RA) or other syndromes is made to ex- gression. A diagnosis of PMR or RA plain these findings when they occur. could therefore be made in the same pa- In a prospective follow-up study on 177 tient at different times depending on the patients we determined the frequency clinical expression of the disease. How- and the characteristics of distal muscu- ever, we feel that these manifestations loskeletal manifestations in PMR (6). represent part of the broader clinical Distal findings occurred in approximate- spectrum of PMR. ly half of these cases of PMR. They were In addition to peripheral joint synovitis,

S-51 Distal findings in polymyalgia rheumatica / C. Salvarani et al. an acute carpal tunnel syndrome with ting edema (RS3PE) syndrome. This PMR and RS3PE syndrome and some clinical evidence of wrist flexor tenosy- condition was described by McCarty in cases of seronegative RA in the elderly, novitis was observed in 14% of the pa- 1985 (13) as being characterized by an and may have important implications for tients (6). Moreover, a well-defined dis- acute onset bilateral symmetrical syno- a reclassification of inflammatory arth- tal tenosynovitis was recorded in 3%. vitis involving predominantly the wrist, ritis in older persons. The sites of tenosynovial the carpus, the small hand joints, and the In summary, distal musculoskeletal ma- were the extensor hand , peroneal flexor digitorum sheaths, associated with nifestations are common in PMR. Peri- tendons and posterior tibial . marked pitting edema of the dorsum of pheral synovitis is most frequent, but di- Distal extremity swelling with pitting the hand. Patients are persistently serone- stal symptoms of diverse types such as edema over the dorsum of the hands and gative for rheumatoid factor and the ar- carpal tunnel syndrome, isolated tenosy- wrists, the ankles, and the tops of the feet ticular complaints respond rapidly to novitis and distal pitting edema often oc- was present in 12% (6). It might be ei- small doses of corticosteroids. cur. Physicians need to be aware of these ther unilateral or bilateral with predomi- We performed a 5-year prospective fol- various manifestations in order to make nant involvement of the upper limbs. The low up study to investigate the relation- a prompt and correct diagnosis and in- distribution of edema was prevalently ship between "pure" RS3PE syndrome, stitute early the appropriate therapy. along the course of the tenosynovial and PMR with and without distal pitting structures (11). Hand and foot magnetic edema (14). No significant differences References resonance imaging (MRI) confirmed the in the demographic, clinical, immunoge- 1. CHUANG T-Y, HUNDER GG, ILSTRUP DM, clinical impression that inflammation of netic and MRI features were found be- KURLAND LT: Polymyalgia rheumatica: A 10- the tenosynovial sheaths is the hallmark tween 23 patients with "pure" RS3PE, year epidemiologic and clinical study. Ann In- tern Med 1982; 97: 672-80. of this condition. Joint synovitis was 156 patients with PMR without pitting 2. HEALEY LA. Long-term follow-up of poly- more difficult to appreciate at clinical ex- edema and 21 patients with PMR with myalgia rheumatica: Evidence for synovitis. amination due to the extensive swelling pitting edema. Semin Arthritis Rheum 1984; 13: 322-8. involving the hands and feet. However, These similarities and the concurrence 3. SALVARANI C, MACCHIONI L, BOIARDI L: Polymyalgia rheumatica. Lancet 1997; 350: hand MRI through the metacarpophalan- of the two syndromes suggest that these 43-7. geal joints also showed the presence of conditions may constitute part of the 4. BRUCE W: Senile rheumatic gout. BMJ 1888; joint effusion (Fig. 1) (7,12). same disease and that the diagnostic la- 2: 811-3. All distal symptoms responded promptly bels of PMR and RS3PE syndrome may 5. HAMRIN B: Polymyalgia arteritica. Acta Med Scand 1972; (Suppl. 533): 1-164. to corticosteroids. No evidence of joint not indicate a real difference. 6. SALVARANI C, CANTINI F, MACCHIONI L, et deformities, erosions, or the develop- Therefore, the involvement of extra-ar- al.: Distal musculoskeletal manifestations in ment of RA was observed during the 39- ticular synovial structures is a predomi- polymyalgia rheumatica. A prospective follow- month follow-up period. nant part of the distal inflammatory pro- up study. Arthritis Rheum 1998; 41: 1221-6. 7. SALVARANI C, CANTINI F, OLIVIERI I, HUN- Distal swelling and edema observed in cess of PMR. This distinctive pattern of DER GG: Polymyalgia rheumatica: A disorder

PMR patients are similar to those obser- extensive, self-limiting inflammation of of extraarticular synovial structures ? J Rheum- ved in patients with remitting, serone- extra-articular synovial membranes may atol 1999; 26: 517-21. gative, symmetrical synovitis with pit- represent the common link between 8. HEALEY LA, SHEETS PK: The relation of poly- myalgia rheumatica to rheumatoid arthritis. J Rheumatol 1988; 15: 750-2. 9. HEALEY LA: Polymyalgia rheumatica and se- ronegative rheumatoid arthritis may be the same entity. J Rheumatol 1992; 19: 270-2. 10. SALVARANI C, HUNDER GG: Musculoskeletal manifestations in a population-based cohort of patients with . Arthritis Rheum 1999; 42: 1259-66. 11. SALVARANI C, GABRIEL S, HUNDER GG: Di- stal extremity swelling with pitting edema in polymyalgia rheumatica. Report of nineteen cases. Arthritis Rheum 1996; 39: 73-80. 12. OLIVIERI I, SALVARANI C, CANTINI F: Remit- ting distal extremity swelling with pitting edema: A distinct syndrome or a clinical fea- ture of different inflammatory rheumatic dis-

eases ? J Rheumatol 1997; 24: 249-52. Fig. 1. An axial T2 weighted section 13. MCCARTY DJ, O'DUFFY JD, PEARSON L, through the metacarpophalangeal HUNTER JB: Remitting seronegative symme- joints shows fluid collection in the trical synovitis with pitting edema: RS3PE flexor synovial sheaths of the third syndrome. JAMA 1985; 254: 2763-7. digit of the right hand (curved arrow) 14. CANTINI F, SALVARANI C, OLIVIERI I, et al.: and joint effusion of the correspon- Remitting seronegative symmetrical synovitis ding joint (large and small arrow- with pitting oedema (RS3PE) syndrome: a pro- heads). spective follow up and magnetic resonance imaging study. Ann Rheum Dis 1999;58:230-6.

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