Letter to the Editor (Submitted on October 2003, not accepted)
British Journal of Rheumatology
Dry eyes and mouth syndrome or sicca, asthenia and polyalgia syndrome ?
Most
patients previously diagnosed as Fibromialgia probably have Joint Hypermobility
Syndrome.
Sir, we have read the interesting notes regarding the paper by Price and Venables in relation to the proposed names for the dry eyes and mouth syndrome (DEMS)1 by Mariette and colleagues2. They have seen similar patients and have proposed the term: sicca, asthenia and polyalgia syndrome (SAPS). Their criteria for the syndrome will be useful for anybody considering this diagnosis.
We agree with both groups that these patients are frequently seen in our rheumatological clinics and that they carry often a wrong diagnosis. To us, they are part of a bigger group of patients that constitute the Joint Hypermobility Syndrome (JHS). Grahame3 has made this diagnosis easier by validating the Brighton Criteria.
In Santiago, Chile, during the last three years we have diagnosed more than 200 JHS patients, looking carefully for them (high index of suspicion) and using the Brighton Criteria. In this group of patients, we frequently have seen patients with the characteristics described for the DEMS/SAPS syndrome. JHS is part of a broader group of patients namely the Hereditary Diseases of the Collagen Tissues. (HDCT). This group accounts for 34% of our rheumatological patients at Clinica Arauco. This very high prevalence of a condition that is not usually diagnosed, even by good rheumatologists, deserves further attention. This really is an emergent disease that has been noted worldwide, when looked for. Guma in Barcelona, Spain has reported lately joint hypermobility in 25% of their rheumatological patients4.
Our opinion that the DEMS/SAPS syndrome patients are part of the HDCT is based on the following facts:
1.- Primary Sjögren is seen frequently in these patients, without immunologic signs or symptoms and with normal immunologic laboratory tests.
2.- They frequently have asthenia/chronic fatigue syndrome which we think is due to Disautonomia. Due to the simpatico-vagal imbalance they are hypotensive, have cold intolerance, dizziness and can have occasional syncopal episodes. The diagnosis can be confirmed with a Tilt Test.
3.- As a consequence of their chronic pain and the fact that their illness is not well recognized by physicians and peers and there is no definite treatment, is that they develop anxiety and depression, as noted by Bulbena5.
We think that these patients do not have primarily a psychosomatic problem, as suggested by Mariette et al., but this is a secondary phenomenon. Our opinion is that they are part of the HDCT and the genesis of the problem is congenital. This group includes the classical forms of Ehlers-Danlos, Marfan Syndrome and Osteogenesis Imperfecta, as well as forme fruste. They have Autosomal Dominant inheritance, but this by itself cannot explain the tremendous increase in prevalence, in the last several decades. We have proposed 6 that most likely the increased prevalence is due to lack of folic acid during pregnancy. It is well known that this is the cause of Neural Tube defects and other congenital abnormalities7. It is probable that the development of these abnormalities is caused by the alteration of the collagen tissues. This same alteration would produce the HDCT, including the BJHS, which to most authors, is the same as the Ehlers-Danlos type III (Hypermobile). It is easy to understand, that the lack folic acid during the peri-conception period can produce alteration of the genes, since it is essential in the synthesis of purinic and pyrimidinic bases of diverse amino acids and consequently is necessary for the synthesis of DNA and RNA. Folic acid antagonists drugs, that act as dihydrofolate reductase inhibitors (Triamterene, Sulfazalazine, anti-epileptics, etc.) when used during the periconceptional period, can have the same effect as lack of folic acid8. As rheumatologists we now that Methotrexate reduces folic acid and is teratogenic. We should remember too that Sulfazalazine can do the same.
We agree with Erhlich 9 that the diagnosis of Fibromialgia is not a good diagnosis. It is our contention that patients with the diagnosis of Chronic fatigue syndrome or Fibromialgia are the same patients that we diagnose as JHS. To us, there is no coincidence that the “tender points sites” described for Fibromialgia, are exactly the areas of entesis, tendinitis and bursitis, which are recurrent problems in patients with JHS. Further more, the fatigue that many of these patients experience at mid-day or after standing or walking slowly, is most likely related to Disautonomia, secondary to JHS.
Now by enriching flour and giving extra folic acid to women during the fertile years, we will see a reduction not only of Neural Tube Defects and other congenital abnormalities (cardiac, renal, etc) but also of HDCT, JHS and DEMS/SAPS. If our hypothesis is correct, it is possible that we will see a reduction of Fibromialgia as well.
References:
1.- Price EJ, Venables PJW, Dry eyes and mouth-
A sub group of patients presenting with sicca symptoms. Rheumatology 2002;41:416-22.
2.- Gaudmont C, Desmoulins F, Bergé E, Mariette X. Diminution importante de la qualité de vie chez les patients porteurs d´un síndrome de Sjogren ou d´un síndrome sec. Rev Rhum 2001;68:990 (C64).
3.- Grahame R, Bird HA, Child A et al. The British Society for Rheumatology Special Interest Group on
Heritable Disorders of Connective Tissue criteria for the benign joint
hypermobility syndrome. The revised
(Brighton 1998) criteria for the diagnosis of BJHS. J Rheumatol
2000; 27: 1777-79
4.- Guma M, Olivé A, Holgado S, Casado E, Roca J, Forcada J, Duró JC y Tena X Una estimación de la laxitud articular en la consulta externa. Rev Esp Reumatol 2001; 28: 298-00.
5.- Bulbena A,
Duró JC, Mateo A, Porta M, Vallejo J: Joint hypermobility syndrome and anxiety
disorders. Lancet
1988; 2: 694
6.- Bravo JF, Arteaga MP, Coello L. Utility of Bone Cintigraphy in the study of Hereditary Disorders of the Connective Tissues (HDCT). Alasbimn J 6(22): October 2003. http://www2.alasbimnjournal.cl/alasbimn/CDA/sec_b/0,1206,SCID%253D5996,00.html
7.- Mulinare J, Cordero JF, Erickson JD, Berry RT. Periconceptional use of multivitamins and the occurrence of Neural Tube Defects. JAMA 1988;260:3141.
8.- Hernandez-Diaz S, Werler MM, Walker AM, Mitchel AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343: 1608-14.
9.- Ehrlich GE. Fibromialgia is not a diagnosis: comment on the editorial by Crofford and Clauw. Arthritis Rheum 2003; 48 (1): 276; author reply 277.
I declare no conflict of interest
Key Message: DEMS and SAPS appear to be part of HDCT, including JHS. Thus, Fibromialgia would not be a good diagnosis, since most patients with such condition most likely have JHS.
Jaime F Bravo MD
Rheumatology Departments
Clinica Arauco and San Juan de Dios Hospital
Santiago, Chile
October 3, 2003