Behçet’s disease associated with malignancies. Report of two cases and review of the literature V.G. Kaklamani1, A. Tzonou2, P.G. Kaklamanis3 1Feinberg School of Medicine, Northwest- ABSTRACT Introduction ern University, Chicago, USA; 2Depart- Objective. To investigate the incidence Behçet’s disease (BD) is a chronic, re- ment of Hygiene and Epidemiology, Med- of malignancies in a cohort of Behçet’s lapsing multi-system disorder. T h e ical School, Athens University, Greece; disease patients and review the world principal manifestations are: oral apht- 3Department of Rheumatology, Athens Medical Center, Athens, Greece. literature. hous ulcers, genital ulcers, skin lesions, Methods. Our database of 128 patients eye, joint, neurological and vascular Vir ginia G. Kaklamani, MD, DSc, As s i s t a n t Professor in Haematology/Oncology; was searched and the age standardized manifestations (1-3). Rare clinical find- Anastasia Tzonou, Associate Professor, rate (ASR) for cancer was calculated. ings include: cardiac, pulmonary and De p a r tment of Hygiene and Epidemiology; F u rt h e r m o re, we performed a MED - renal disorders (1-3), as well as, epidi- Phaedon G. Kaklamanis, MD, Emeritus LINE search from 1970 through 2003, dymoorchitis (4). The epidemiology of Professor of Internal Medicine. as well as, a search in the proceedings BD in most parts of the world has re- Please address correspondence to: of international conferences for cases cently been reviewed (5-7). The patho- Phaedon Kaklamanis, MD, 61 Ipsilantou of malignancies associated with Beh - genesis of the disease has not been elu- St., Athens 11521, Greece. çet’s disease. cidated (1,2,8), although genetic fac- E-mail: Virginia @hol.gr Results. Two of our 128 patients with tors, environmental agents and immune Received on September 30, 2004; accepted B e h ç e t ’s disease were found to have aberrations have been implicated (1, 2, in revised form on April 1, 2005. solid tumors. One male had lung can - 9). Immune abnormalities, particularly Clin Exp Rheumatol 2005; 23 (Suppl. 38): cer and the other female had kidney increased production of some antibod- S35-S41. cancer. The ASR for cancer cases in ies have been reported in patients with © Copyright CLINICALAND EXPERIMEN- our population was investigated and it BD (9). However, Raynaud’s phenom- TAL RHEUMATOLOGY 2005. was found to be 1,600 per 100,000 in enon, polyserositis, Sjögren’s syndro- Key words: Behçet’s disease, 10 years. The ASR for cancer cases in me, neutrophil, antiphospholipid and malignancies. Greece according to WHO is 272.51 antinuclear antibodies, which charac- per 100,000 per year and there f o re terize an autoimmune disease, have not 2,725 per 100,000 in 10 years. been associated with BD (10,11). Sev- In the world literature 112 cases of ma - eral studies have shown that arterial and lignancies associated with Behçet’s di - venous involvement of all size vessels sease were found: Sixty five cases were are characteristic findings of the dis- of male patients and 46 of female with ease (12-16). Given the above vas- 1 case of unknown gender. The solid culitic manifestations, BD is classified malignancies associated with Behçet’s among the wide spectrum of systemic disease included cases of bladder, vasculitides (14). b reast, uterus, thyroid and stomach In autoimmune and vasculitic disorders cancer, whereas haematological malig - the risk of malignancies has been ex- nancies included leukemia, myelodys - tensively studied. In patients with rheu- plastic syndrome, lymphoma, multiple matoid arthritis (RA), both solid and myeloma, Hodgkin’s disease and lym - haematopoietic malignancies have been phosarcoma. The treatment administer - reported (17,18). In Western Europe ed in these patients with their disease is and in the United States the risk is re- also reported. lated primarily to the development of Conclusion. The age standardized rate haematopoietic neoplasms, whereas in of cancer in our population was lower Japanese patients oropharyngeal malig- than that of the general population in nancies are more commonly seen (19). G reece, although the difference was The discrepancy may have to do with not statistically significant. However, environmental and dietary differences there is discrepancy in the world litera - between the different regions. Patients ture and the possibility of development with systemic lupus erythematosus of malignancies in Behçet’s disease pa - (SLE) have increased risk of develop- tients should not be ignored. ing both solid tumors and haematologic S-35 Behçet's disease and malignancies / V.G. Kaklamani et al. malignancies (19-23). In patients with genital ulcers appeared. These lesions of search headings of «Behçet’s dis- progressive systemic sclerosis (sclero- were recurrent. Pathergy test was posi- ease», «Behçet’s syndrome», «Adaman- derma) increased risk of malignancy tive and the diagnosis of BD was estab- tiades-Behçet’s disease», «cancer» and was found (24), particularly bronchoal- lished. He was treated with colchicine «malignancy». Cases from proceedings veolar carcinoma (23). The incidence and prednisolone 30 mg/d which was of international conferences in BD of malignancy in dermatomyositis and tapered slowly to 7.5 mg/d. Since then were also included in the analysis. polymyositis (DM,PM) has been the every 3-4 months most of the clinical subject of multiple publications (25- manifestations would recur and the Statistical section 29). Among 618 patients with DM and dose of prednisolone would be increas- We wanted to determine whether the PM, 198 cases of cancer were reported ed. The time of cancer diagnosis he incidence of malignancy in our BD pop- (26), pointing toward a predisposition presented with small oral aphthae, one ulation was similar to that of the gener- to the development of malignant disor- genital ulcer and arthritis of the right al population. For this we had to stan- ders in such patients. Wegener’s granu- knee. In March 1999 he presented with dardize our population since the age di- lomatosis (30), Henoch-Schönlein pur- neurological symptoms and a brain stribution of our population was not si- pura (31) and other vasculitides (32) MRI showed a solid mass measuring milar to that of the general population. have also been associated with increas- 3.5 cm at the lower left parietal area. We calculated the age standardized rate ed risk of malignancies. In BD patients This was a metastatic tumor originating (ASR) for cancer cases in our popula- more than hundred cases associated from his lung and a biopsy of the lung tion which was 1,600 per 100,000 in 10 with malignancies have been publish- tumor showed to be a microcytic type years. We used the following formula ed. However, the direct relationship adenocarcinoma with large cells. The for calculating ASR: ASR = S cases with BD has not been proved. patient was treated with carboplatin, (age group)/population (age group) x The development of malignancies in paclitaxel and radiotherapy. Several 100,000 world standard population autoimmune diseases and vasculitides months later he died. The patient devel- (age group)/world standard population. could be related to abnormalities in im- oped lung cancer 10 years after the According to the WHO the ASR for mune regulation, T cell deficiency, or diagnosis of BD. He had a 40 pack/year cancer cases in Greece is 272.51 per the overproliferation of B cells, which smoking history. 100,000 per year and therefore 2.725 may trigger a malignant transformation per 100,000 in 10 years (36). After per- of cells (33). The association of malig- Case 2 forming a c 2 test to assess the signifi- nancies with BD may represent a para- A 60-year-old housewife at the age of cance, we found that there was no sta- neoplastic syndrome (34) or may be re- 17 developed oral and genital ulcers. tistically significant difference between lated to the above mentioned distur- They were followed by arthritis of the the two populations. Furthermore, we bances (33). Furthermore, medications lower extremities. At the age of 20 calculated the annual incidence of ma- that BD patients are chronically on those symptoms recurred several times lignancy in our population of 128 pa- may also predispose to the develop- and anterial uveitis was diagnosed. tients with BD and found it to be 156 in ment of neoplastic diseases. Five years later erythema nodosum and 100,000. Our primary aim in this report is to recurrences of oral and genital ulcers share our own experience on the asso- developed. Pathergy test was negative Review of the literature ciation of malignant neoplasms and BD and she had HLA B5 (51). The dia- A variety of solid tumors have been re- by searching our database of 128 pa- gnosis of BD was established and be- ported in the world literature including tients with a median follow up of 10 gan treatment with prednisolone 30 two of our own. The diagnosis of BD years. Furthermore, we will review the mg/d and chlorambucil 6-10 mg/d for 3 was established according to the crite- cases of malignancies associated with years. Two years later hypopyon iritis ria reported (96). In a few cases the dis- BD present in the scientific literature. was diagnosed and received predni- ease onset was defined as the time solone 20 mg/d and azathioprine 100- when the patient developed the first Material and methods 200 mg/d for 8 years. At the time of symptom, while in others when the dia- Our BD patient cohort has been pros- diagnosis of cancer she suffered from gnostic criteria were fulfilled. pectively collected since 1990, during chronic uveitis, recurrent erythema no- which time we have enrolled 128 pa- dosum and oral aphthae. At the age of 1.