Letters to the Editors

Signifi cant improvement of axillary artery stenosis in a ▼ 67-year-old woman with giant ▼ cell ▼

Sirs, We describe a 67-year-old woman with arteritis (GCA) presented with a month’s history of intermittent claudica- tion of the upper limbs and newly appeared Raynaud’s phenomenon. The patient did not complain of , or pel- vic pain, nor did she have jaw or . Her past medical history was unremarkable. ▼ The physical examination revealed absence ▼ of radial and brachial pulses bilaterally. ▼ Temporal arteries appeared normal on ex- amination. Blood pressure was unrecordable in the upper limbs. The laboratory evalua- tion showed high erythrocyte sedimentation rate (ESR) (70 mm/h) and C-reactive pro- tein (CRP) (80 mg/dl), as well as hypochro- mic and microcytic anemia (Hemoglobin 8.8 gr/dl). The rest of the laboratory tests were within normal limits. The color Dop- Fig. 1. Doppler studies showed right axillary artery stenosis (A) and left axillary artery stenosis (B). After pler ultrasound study revealed a signifi cant a year of treatment a signifi cant degree of improvement were noted of both axillary arteries (C and D respectively). degree of bilateral axillary artery stenosis with excessively thickened endothelium Color Doppler ultrasonography demon- enables a good clinical response and avoid- Fig. 1A and B). The angiography of the aor- strates a characteristic picture in GCA show- ance of large-artery complications. tic arch and its branches also showed exten- ing a hypoechoic mural thickening in the sive smooth appearance of stenoses of the acute phase of the disease due to edema of C.G. PAPADOPOULOS1, MD axillary arteries bilaterally. The of the vessel wall with subtotal or total occlu- P.V. VOULGARI1, MD A. ZIOGA2, MD the left temporal artery revealed histologi- sion of the involved vessel. In the chronic 1 cal lesions suggesting GCA. stage or after treatment, the mural thicken- G.A. MILTIADOUS , MD, P. NICOLOPOULOS3, MD, Treatment with 60 mg/day and ing becomes hyperechoic due to fi brosis. M.S. ELISAF1, MD, Prof. methotrexate (MTX) 10 mg/week was start- Thus, Doppler ultrasonography permits ac- A.A. DROSOS1, MD, FACR, Prof. ed Four weeks later, the ESR and CRP had curate assessment of the involved vessels at Departments of 1Internal Medicine, 2Pathology fallen to normal values (ESR 3 mm/h, CRP specifi c sites (4). and 3Radiology, Medical School, University of 1 mg/dl). and hemoglobin also returned to Angiography, computed tomography, and Ioannina, Ioannina, Greece. normal values, so the dose of prednisolone magnetic resonance angiography delineate Address correspondence and reprint requests to: was tapered. One year later, her symptoms characteristic patterns in large-vessel GCA Alexandros A. Drosos, MD, FACR, Department improved impressively, the blood pressure (5). of Internal Medicine, Medical School, was recordable in both limbs and the color High-dose of is the treatment University of Ioannina, 45110 Ioannina, Greece. Doppler ultrasound studies showed a sig- of choice for large-vessel GCA (2). Early E-mail: [email protected] nifi cant improvement of the axillary artery diagnosis and treatment enables a good Competing interests: none declared. stenosis (Fig. 1C and D). At this time the response avoiding vascular complications. dose of prednisolone was 10 mg every other However, angioplastic revascularization is References day plus 10 mg MTX/week. required in cases with arterial occlusion not 1. NUENNINGHOFF DM, HUNDER GG, CHRISTIAN- GCA targets extracranial branches of the responsive to therapy, while SON TJ, MCCLELLAND RL, MATTESON EL: Incid- carotid arteries preferentially but also af- the addition of may help maintain- ence and predictors of large-artery fects the large arteries and especially the ing the angioplastic results (6). Despite a (, , and/or large- artery stenosis) in patients with : carotid, subclavian, and axillary arteries in tendency to restnoses, balloon angioplasty a population-based study over 50 years. Arthritis almost a quarter of patients (1). The clini- of the upper-extremity artery, in combina- Rheum 2003; 48: 3522-31. cal presentation of the large vessel involve- tion with immunosuppressive treatment, is 2. VAN DAMME H, FOURNY J, ZICOT M, LIMET R: ment includes claudication of the arms, ab- an effi cient method for the treatment of ex- Giant cell arteritis (Horton’s disease) of the axillary sent or asymmetrical pulses, paresthesias, tracranial GCA (7, 8). Although the use of artery--case reports. Angiology 1989; 40: 593-601. Raynaud’s phenomenon and occasionally, MTX in temporal arteritis is controversial, 3. LONG A, BRUNEVAL P, LAURIAN C, CORMIER JM, CAMILLERI JP, FIESSINGER JN: Extratem- peripheral gangrene (2, 3). Patients with the it seems to be an effective corticosteroid- poral Horton’s disease: diagnosis using subclavian large-vessel variant of GCA may lack the sparing agent for the treatment of GCA (9, biopsy. 4 cases. Arch Mal Coeur Vaiss 1989; 82: clinical evidence of cranial involvement, 10). However, the most important fi nding 1727-31. as happened with our patient. Almost 50% in this case is the signifi cant improvement 4. SCHMIDT WA, KRAFT HE, BORKOWSKI A, of temporal artery are negative for of axillary artery stenosis after a year of GROMNICA-IHLE EJ: Color duplex ultrasonog- early treatment with and MTX. raphy in large-vessel giant cell arteritis. Scand J . In addition, large artery involve- Rheumatol 1999;1999; 228:8: 3374-6.74-6. ment in GCA may be complicated by aortic Thus, in patients with upper limb , 5. AGARD C, PONGE T, FRADET G et al.: Giant cell aneurysm, artery stenosis and/or aortic dis- the possibility of large-vessel GCA must be arteritis presenting with aortic dissection: two cases section increasing mortality (1). considered. Early diagnosis and treatment and review of the literature. Scand J Rheumatol

S-151 Letters to the Editors

2006; 35: 233-6. count of 357x103/mm3. Serum IgA were L. CANTARINI1, MD, PhD 6. AMANN-VESTI BR, KOPPENSTEINER R, RAIN- slightly increased. C-reactive protein, eryth- A. BROGNA2, MD 3 ONI L, PFAMATTER T, SCHNEIDER E: Immediate rocyte sedimentation rate, kidney function A. FIORAVANTI , MD and long-term outcome of upper extremity balloon M. GALEAZZI1, MD, Prof. angioplasty in giant cell arteritis. J Endovasc Ther and urine sediment were normal. Antistrep- 1 2003; 10: 371-5. tolysin was not increased. Antinuclear anti- Interdepartmental Research Center of Systemic 7. BOTH M, ARIES PM, MULLER-HULSBECK S et al.: Autoimmune and Autoinfl ammatory Diseases, bodies, cryoglobulins and antineutrophilic 2 Balloon angioplasty of arteries of the upper extrem- Unit of , Department of cytoplasmic (perinuclear and Paediatrics, Obstetrics and Reproductive ities in patients with extracranial giant-cell arteritis. cytoplasmic patterns) were negative. Ann Rheum Dis 2006; 65: 1124-30. Medicine, Neonatal Intensive Care Unit, 3 8. BOTH M, JAHNKE T, REINHOLD-KELLER E et al.: The patient had started treatment with pi- Department of Clinical Medicine and Percutaneous management of occlusive arterial dis- dotimod 400 mg per day eight days before Immunologic Sciences, Unit of Rheumatology, ease associated with vasculitis: a single center experi- her visit due to recurring tonsil Policlinico Le Scotte, University of Siena, ence. Cardiovasc Intervent Radiol 2003;2003; 226:6: 119-26.9-26. and adenoid-tonsillar hypertrophy. Siena, Italy. 9. HOFFMAN GS, CID MC, HELLMANN DB et al.: She had had her last three months Address correspondence and reprint requests to: A multicenter, randomized, double-blind, placebo- earlier, and she was living with her parents Luca Cantarini, MD, Institute of Rheumatology, controlled trial of adjuvant methotrexate treatment Policlinico “Le Scotte”, University of Siena, for giant cell arteritis. Arthritis Rheum 2002; 46: who were in good health. Viale Bracci 1, 53100 Siena, Italy. 1309-18. Pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidi- E-mail: [email protected] 10. DASGUPTA M, HASSAN N; BRITISH SOCIETY nyl) carbonyl]-thiazolidine-4-carboxylic Competing interests: none declared. FOR RHEUMATOLOGY GUIDELINES GROUP: Gi- acid, PGT/1A, CAS 121808-62-6) is a syn- ant cell arteritis: recent advances and guidelines for thetic biological response modifi er which management. Clin Exp Rheumatol 22007;007; 2255 ((Suppl.Suppl. References 44): S62-5. acts by stimulating cell-mediated immunity 1. CALVINO MC, LLORCA J, GARCIA-PORRUA C, (5) and which has been shown to enhance FERNANDEZ-INGLESIAS JL, RODRIGUEZ-LEDO several immune parameters in humans, P, GONZALEZ-GAY MA: Henoch-Schönlein pur- both in vitro and in vivo (6, 7). Pidotimod pura in children from northwestern Spain: a 20-year is active on T-lymphocytes in early matura- epidemiologic and clinical study. Medicine 2001; tion stage (8) and is able to enhance periph- 80: 279-90. Henoch-Schönlein purpura 2. TRAPANI S, MICHELI A, GRISOLIA F et al.: associated with pidotimod eral blood mononuclear cell proliferation Henoch-Schönlein purpura in childhood: epidemio- through an increased -2 produc- logical and clinical analysis of 150 cases over a 5- therapy tion (IL-2) (7). IL-2 has been shown to in- year period and review of literature. Semin Arthritis duce interleukin-5 (IL-5) production by T- Rheum 2005; 35: 143-53. Sirs, lymphocytes, in a dose-dependent manner, 3. SAULSBURY FT: Henoch-Schönlein purpura. Curr Henoch-Schönlein purpura (HSP) is a Opin Rheumatol 2001;2001; 113:3: 335-40.5-40. and IL-5 induces IgA production from B- 4. SAULSBURY FT: Clinical update: Henoch-Schön- small-sized vasculitis affecting mainly lymphocytes and is also recognized by its lein purpura. Lancet 2007; 369: 976-8. children and young adults. The mean age activity as an IgA-enhancing factor (9). 5. COPPI G, MANZARDO S: Experimental immuno- of patients is six years; 90% of patients are She was diagnosed with drug related HSP logical screening tests on Pidotimod. Arzneimittel- under ten years of age (1, 2). and discontinuation of the drug led to a forschung 1994; 44:1411-6. A wide variety of drugs, pathogens and oth- complete resolution of the disease; abdomi- 6. PUGLIESE A, GIRARDELLO R, MARINELLI L, FORNO B, PATTARINO PL, BIGLINO A: Evaluation er environmental exposures have been asso- nal pain was resolved in four days, purpuric of Pidotimod effects on some immune parameters. ciated with HSP. Although the precise eti- rash disappeared within ten days and arthri- J Chemother 1991; 3: 144. ology of the disease is unknown, it is clear tis improved over the following two weeks. 7. AUTERI A, PASQUI AL, GOTTI G et al.: The effect that antigenic stimuli causing elevation of The occurrence of HSP was probably re- of a new biological response modifi er (Pidotimod) circulating Immunoglobulin A (IgA) have a lated to pidotimod therapy. on surgery-associated immunodefi ciency. Int J Im- pivotal role in the pathogenesis of HSP (3). There was a close temporal relationship munotherapy 1993; IX: 95. 8. BENETTI GP, FUGAZZA L, STRAMBA BADIALE The clinical manifestations of HSP are a between drug ingestion and onset of symp- M et al.: Ex vivo evaluation of pidotimod activity consequence of widespread vasculitis re- toms and when its intake was interrupted on cell-mediated immunity. Arzneimittelforschung sulting from IgA deposition in vessel walls the patient’s clinical picture improved. 1994; 44: 1476-9. and the renal mesangium (3, 4). HSP is For this reason, and on the basis of the 9. KURAOKA M, HASHIGUCHI M, HACHIMURA S, - - - + characterized by palpable, non-thrombocy- Naranjo algorithm (10), adverse drug reac- KAMINOGAWA S: CD4 c-kit CD3ε IL-2Rα Pey- er’s patch cells are a novel cell subset which secrete topenic purpura, arthritis and/or arthralgia, tion could be considered possible and we IL-5 in response to IL-2: implications for their role abdominal pain, gastrointestinal haemor- believe that our patient may represent the in IgA production. Eur J Immunol 22004;004; 334:4: 11920-920- rhage and/or nephritis (2). fi rst clear evidence of a relationship be- 9. We report the fi rst case of HSP associated tween HSP and pidotimod treatment. 10. NARANJO CA, BUSTO U, SELLERS EM et al.: with treatment with pidotimod. Although this is the fi rst report of HSP as- A method for estimating the probability of adverse A nine-year-old female came under our sociated with pidotimod, clinicians should drug reactions. Clin Pharmacol Ther 1981; 30: 239- 45. observation in January 2007 for a non-pru- be aware of a possible association between ritic palpable purpuric rash with lower limb HSP and the intake of pidotimod; it is also predominance, diffuse abdominal pain and possible that the intake of cell mediated arthritis involving knees and ankles; the ar- immunity stimulating drugs may trigger thritis was painful and inhibited walking. the development of cell mediated immu- Laboratory analysis showed a white blood nity diseases in genetically predisposed cell count of 8.45x103/mm3 and a patients.

S-152