Kashin-Beck disease

Infobox_Disease
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Caption = Patient diagnosed with Kashin-Beck Disease
DiseasesDB = 30038
ICD10 = ICD10|M|12|1|m|05
ICD9 = ICD9|716.0
ICDO =
OMIM =
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The Kashin-Beck disease (KBD) is a permanent and disabling osteoarticular disease involving growth and joint cartilage. Clinical manifestations appear at the age of 5 years. An increasing number of joints become affected during childhood and up to the age of 25 years. Affected individuals present with joint destruction which produces recurrent and mainly bilateral joint pain, with restriction of movement and joint enlargement. The most frequently involved joints are the ankles, knees, wrists and elbows. Severely affected cases are characterised by disproportionate stunted growth with associated joint deformity. Both for adults and children, the resulting disability causes an important human and socio-economic burden in affected villages (Mathieu et al., 1997).

Distribution on Kashin-Beck Disease

Kashin-Beck disease occurrence is limited to 13 provinces and 2 autonomous regions of China. It has also been reported in Siberia and North Korea, but incidence in these regions is reported to have decreased with socio-economic development. In China, KBD is estimated to affect some 2 to 3 million people across China, and 30 million are living in endemic areas. Life expectancy in KBD regions has been reported to be significantly decreased in relation to selenium deficiency and Keshan disease (endemic juvenile dilative cardiomyopathia).

The prevalence of KBD in Tibet varies strongly according to valleys and villages.

Prevalence of clinical symptoms suggestive of KBD reaches 100 % in 5-15 years old children in at least one village. Prevalence rates of over 50% are not uncommon. A clinical prevalence survey carried out in Lhasa prefecture yielded a figure of 11.4% for a study population of approximately 50 000 inhabitants. As in other regions of China, farmers are by far the most affected population group.

Aetiology and risk factors

The aetiology of KBD remains controversial. Studies on the pathogenesis and risk factors of KBD proposed selenium deficiency, inorganic (manganese, phosphate...) and organic matter (humic acids and fulvic acids) in drinking water, fungi on self-produced storage grain (Alternaria sp., Fusarium sp.), producing trichotecene (T2) mycotoxins.

Nowadays, most authors accept that the aetiology of KBD is multifactorial, selenium deficiency being the underlying factor that predisposes the target cells (chondrocytes) to oxidative stress from free-radical carriers such as mycotoxins in storage grain and fulvic acid in drinking water.

In Tibet, epidemiological studies carried out in 1995-1996 by MSF and coll. showed that KBD was associated with iodine deficiency and with fungal contamination of barley grains by Alternaria sp., Trichotecium sp., Cladosporium sp. and Drechslera sp (Chasseur et al., 1997). Indications existed as well with respect to the role of organic matters in drinking water.

A severe selenium deficiency was documented as well, but selenium status was not associated with the disease, suggesting that selenium deficiency alone could not explain the occurrence of KBD in the villages under study (Moreno-Reyes et al., 1998)

Treatment

Treatment of KBD is so far palliative. Surgical corrections have been made with success by Chinese and Russian orthopaedists. By the end of 1992, Médecins Sans Frontières - Belgium started a physical therapy programme aiming at alleviating the symptoms of KBD patients with advanced joint impairment and pain (mainly adults), in Nyemo county, Lhasa prefecture. Physical therapy had significant effects on joint mobility and joint pain in KBD patients. Later on (1994 - 1996), the programme has been extended to several other counties and prefectures in Tibet.

Prevention on Kashin-Beck disease

Prevention of Kashin-Beck Disease has a long history. Intervention strategies were mostly based on one of the three major etiologic theories.

Selenium supplementation, with or without additional antioxidant therapy (Vitamin E and Vitamin C) has been reported to be successful, but in other studies no significant decrease could be shown compared to a control group. Major drawbacks of selenium supplementation are logistic difficulties (daily or weekly intake, drug supply), potential toxicity (in case of less controlled supplementation strategies), associated iodine deficiency (that should be corrected before selenium supplementation in order to prevent further deterioration of thyroid status) and low compliance. The latter was certainly the case in Tibet, where a selenium supplementation has been implemented from 1987 to 1994 in areas of high endemicity.

With the mycotoxin theory in mind, backing of grains before storage was proposed in Guanxhi province, but results are not reported in international literature. Changing from grain source has been reported to be effective in Heilongjang province and North-Korea.

With respect to the role of drinking water, changing of water sources to deep well water has been reported to decrease the X-ray metaphyseal detection rate in different settings.

In general, the effect of preventive measures however remains controversial, due to methodological problems (no randomised controlled trials), lack of documentation or, as discussed above, due to inconsistency of results.

References

* http://www.kbdfoundation.org
* Malaisse F., De Kesel A., Begaux F., Delcarte E., Drokar P., Goyens P., Hinsenkamp M., Leteinturier B., Mathieu F., Ritschen L., Wangla R., Lognay G. A propos des champignons comestibles du Tibet centro-austral (R.P.Chine). [http://www2.geo.ulg.ac.be/geoecotrop/ "Geo-Eco-Trop"] . 2006 ; 28(2) :13-29.
* Moreno-Reyes R, Mathieu F, Boelaert M, Begaux F, Suetens C, Rivera MT, Neve J, Perlmutter N, Vanderpas J. Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy. Am J Clin Nutr. 2003 Jul;78(1):137-44.
* Haubruge, E.; Chasseur, C.; Suetens, C.; Mathieu, F.; Begaux, F.; Malaisse, F.
* Mycotoxins in Stored Barley (Hordeum vulgare) in Tibet Autonomous Region (People's Republic of China) Mountain Research and Development. August 2003, 23 (3):284-87.
* Chasseur, C.; Begaux, F.; Suetens, C.; Mathieu, F.; Nolard, N.; Malaisse, F.; Wang, Z.; Haubruge, E. Is Kashin-Beck disease related to the presence of fungi on grains? 8th Proceedings IWCSPP; July 2002, 526 - 528
* Haubruge E, Chasseur C, Debouck C, Suetens C, Michel V, Mathieu F, Begaux F. Occurrence of mycotoxins in stored barley in Tibet Autonomous Region. Food Addit.Contam., 2001.
* Debouck C, Haubruge E, Bollaerts P, van Bignoot D, Brostaux Y, Werry A, Rooze M. Skeletal deformities induced by the intraperitoneal administration of deoxynivalenol (vomitoxin) in mice. Int Orthop. 2001;25(3):194-8.
* Mathieu F, Suetens C, Begaux F, De Maertelaer V, Hinsenkamp M. Effects of physical therapy on patients with Kashin-Beck disease in Tibet. Int Orthop. 2001;25(3):191-3.
* Suetens C, Moreno-Reyes R, Chasseur C, Mathieu F, Begaux F, Haubruge E, Durand MC, Neve J, Vanderpas J.Epidemiological support for a multifactorial aetiology of Kashin-Beck disease in Tibet. Int Orthop. 2001;25(3):180-7.
* Sudre P, Mathieu F. Kashin-Beck disease: from etiology to prevention or from prevention to etiology?Int Orthop. 2001;25(3):175-9.
* Malaisse F, Haubruge E, Mathieu F, Begaux F. Ethno-agricultural approach to the rural environment in the prevention of Kashin-Beck disease. Int Orthop. 2001;25(3):170-4.
* La Grange M, Mathieu F, Begaux F, Suetens C, Durand MC. Kashin-Beck disease and drinking water in Central Tibet.Int Orthop. 2001;25(3):167-9.
* Moreno-Reyes R, Suetens C, Mathieu F, Begaux F, Zhu D, Rivera T, Boelaert M, Neve J, Perlmutter N, Vanderpas J. Kashin-Beck disease and iodine deficiency in Tibet. Int Orthop. 2001;25(3):164-6.
* Haubruge E, Chasseur C, Debouck C, Begaux F, Suetens C, Mathieu F, Michel V, Gaspar C, Rooze M, Hinsenkamp M, Gillet P, Nolard N, Lognay G. The prevalence of mycotoxins in Kashin-Beck disease.Int Orthop. 2001;25(3):159-61.
* Chasseur C, Suetens C, Michel V, Mathieu F, Begaux F, Nolard N, Haubruge E. A 4-year study of the mycological aspects of Kashin-Beck disease in Tibet. Int Orthop. 2001;25(3):154-8.
* Pasteels JL, Liu FD, Hinsenkamp M, Rooze M, Mathieu F, Perlmutter N. Histology of Kashin-Beck lesions. Int Orthop. 2001;25(3):151-3.
* Hinsenkamp M, Ryppens F, Begaux F, Mathieu F, De Maertelaer V, Lepeire M, Haubruge E, Chasseur C, Stallenberg B. The anatomical distribution of radiological abnormalities in Kashin-Beck disease in Tibet.Int Orthop. 2001;25(3):142-6.
* Mathieu F, Begaux F, Suetens C, De Maertelaer V, Hinsenkamp M. Anthropometry and clinical features of Kashin-Beck disease in central Tibet. Int Orthop. 2001;25(3):138-41.
* Hinsenkamp M. Kashin-Beck disease. Int Orthop. 2001;25(3):133. No abstract available.
* Haubruge E, Chasseur C, Mathieu F, Begaux F, Malaisse F, Nolard N, Zhu D, Suetens C, and Gaspar C. La maladie de Kashin-Beck et le milieu rural au Tibet: un problème agri-environnemental. Cahiers Agricultures 9:117-124, 2000.
* Hinsenkamp M. Kashin-Beck disease. Guest Editorial in "Orthopaedics Today". 2000;3(6):3-6.
* Moreno-Reyes R, Suetens C, Mathieu F, Begaux F, Zhu D, Rivera MT, Boelaert M, Neve J, Perlmutter N, Vanderpas J. Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med. 1998 Oct 15;339(16):1112-20.
* Liu F., Wang Z., Hinsenkamp M. Knee osteotomy in 195 advanced cases of Kashin-Beck disease. Int Orthop. 1998;22:87-91.
* Chasseur C, Suetens C, Nolard N, Begaux F, Haubruge E. Fungal contamination in barley and Kashin-Beck disease in Tibet.Lancet. 1997 Oct 11;350(9084):1074. No abstract available.
* Mathieu F, Begaux F, Lan ZY, Suetens C, Hinsenkamp M. Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet.Int Orthop. 1997;21(3):151-6.