LETTER He` ctor Corominas Æ Josep M. Guardiola Æ Laia Matas Guillermo Va´ zquez Neurofibromatosis and systemic lupus erythematosus. A matter of coincidence? Received: 5 May 2003 / Accepted: 5 May 2003 / Published online: 14 October 2003 Ó Clinical Rheumatology 2003 Neurofibromatosis type 1 (NF1) is an autosomal dom- inant disease that is present in one in 4000 individuals and affects ectodermal and mesodermal tissues. It is well known that patients with neurofibromatosis show an increased incidence of various neoplasms, most of these being tumours of neural crest origin, including neurofi- bromas, leiomyomas, ganglioneuromas, paragangliomas and carcinoids, but it has also been related to small- bowel adenocarcinoma, pancreatic endocrine malignant tumour, and neurofibromatosis of the colon and urinary bladder [1, 2, 3, 4, 5]. Systemic lupus erythematosus (SLE) is an autoimm- mune disease with diverse clinical manifestations and characterised by the production of antibodies to com- ponents of the cell nucleus, mostly present in young females. The disease shows strong familial aggregation, mainly in first-degree relatives [6]. We report a young female patient with SLE and NF1 while considering the interest of such an uncommon association. A 32-year-old woman, diagnosed in 1997 with neu- rofibromatosis type 1 (NF1), presented with numerous cafe-au-lait spots and pedunculated lesions without central nervous system involvement. Genetic study revealed a single mutation in exon 37 of the NF1 gene (679C fi A). In October 2002 she was admitted to our hospital with a history of 1 month of fever together with a symmetrical and bilateral polyarthritis of the knee, ankle, wrist, metacarpophalangeal joints 2 and 3, and all proximal interphalangeal joints (PIP). She also presented with oral ulcers, 30 min morning stiffness, RaynaudÕs phenomenon and alopecia. Physical exami- nation on admission showed tenderness to palpation of the involved joints. Temperature was 38°C, heart rate 96/min. Laboratory studies revealed haemoglobin 13 g/ dI, white blood cell count 6.9·10 9 /l with 3.6·10 9 /l neu- trophils and 0.33·10 9 /l lymphocytes, and erythrocyte sedimentation rate 34 mm/h. Renal and liver function tests were normal. Antinuclear antibodies were >1/320 H, 1/320 S, 1/160 N, positive DNA-EIA and comple- ment levels of C3: 43 mg/100ml (85–193) and C4: 11 mg/ 100ml (12–36). RNP, Sm, Ro and La antibodies were negative. Serologies and microbiological studies for CMV, EBV, CVH, BVH, HV-type 6 toxoplasma and tuberculosis were negative. Based on ACR criteria [7] she was diagnosed with systemic lupus erythematosus (SLE) and treatment with oral hydroxychloroquine and prednisone was begun. The most frequent variant of the group is neurofi- bromatosis type 1 (NF1), which can vary in severity but can affect all organs. The diagnosis of NF1 is based on clinical criteria, but with the development of molecular genetic tests a wide range of mutations have been described, although the large size of the gene has impeded the development of a clinical diagnostic test [8]. The gene for NF1 has been identified by cDNA cloning, and a homology between the NF1 gene product and members of the GTPase-activating protein (GAP) superfamily has been described [9]. The association of NF1 and SLE has been reported elsewhere and it has been debated whether the associa- tion was coincidental or related. The cases described to date showed that SLE was already present when NF1 appeared. The hypothesis that virus infections in SLE patients might play a role in the higher susceptibility to tumours or connective tissue diseases has been sup- ported [10, 11, 12]. In contrast to these reports, our patient was previously diagnosed with NF1, and 6 years later with SLE. No data exist in NF1 patients about their susceptibility to develop SLE. Is that therefore a matter of coincidence? Clin Rheumatol (2003) 22: 496–497 DOI 10.1007/s10067-003-0764-8 H. Corominas (&) Æ J. M. Guardiola Æ L. Matas Æ G. Va´zquez Unitat de Reumatologia, Departament de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Avda. Antoni Ma Claret 167, 08025 Barcelona, Catalonia, Spain E-mail: Hcorominas@hsp.santpau.es Tel.: +34-3-2919343 Fax: +34-3-2919269