Overlap syndrome

The definition of an overlap syndrome dictates that the criteria for diagnosis of both disorders (in the present context, of PM/DM and of some other connective tissue disorder), are fulfilled. It is not unexpected that those syndromes which overlap with PM/DM are also either known autoimmune conditions or ones in which an autoimmune basis is strongly suspected. The association of these disorders with PM/DM syndromes may not materially alter the basic histopathological featmes expected in PM/DM but some differences may be identifiable. The disorders most frequently associated with an overlap syndrome are rheumatoid arthritis, systemic lupus erythematosis, scleroderma, and mixed connective tissue disease. 

MELAS cases. Ragged red fibers, common to MELAS, myoclonic epilepsy with ragged red libers, Keams-Sayre, and overlap syndromes, reflect proliferation of abnormal mitochondria under the sarcolemma. However, some patients with MELAS do not develop such a proliferation of abnormal subsarcolemmal mitochondria, so a negative muscle biopsy finding, particularly early in the course of disease progression, does not preclude consideration of this syndrome. 

The distinction between primary biliary cholangitis and primary or secondary sclerosing cholangitis by differential diagnosis may be made substantially more difficult at times owing to special courses of disease, autoimmune hepatitis or overlap syndromes. 

In view of the variety of possible immunological reactions directed towards the canaliculi or bile-duct epithelia and the difficulties involved in making a definitive histological diagnosis and classification, it would be feasible to include a so-called overlap syndrome or conversion syndrome in the hypothesis of autoimmune cholangitis. 

AIH/PBC This form usually develops in adults only, because children are not affected by PBC. Such an overlap syndrome can occur as two different variants ... 

Regarding the therapeutic effects, it is per se unimportant whether the existing overlap is a coincidence, a subsequent sequela or a real overlap syndrome every PBC or PSC with the criteria of AIH requires immunosuppressive therapy. 

A progressive course of disease results in biliary cirrhosis, which does not, however, reveal whether the original diagnosis was PBC, PSC or AIH, or even an overlap syndrome. 

In the presence of an overlap syndrome (or a conversion syndrome), the therapy concept depends on the respective predominant component, which as a rule is AIH. Consequently, prednisolone + UDCA or prednisolone + azathioprine + UDCA are applied. 

Immunologic reactions Primary biliary cholangitis, primary sclerosing cholangitis, overlap syndromes, allograft rejection, sarcoidosis, etc. are worth mentioning in this context. 

ChazouillCTes, O., Wendum, D., Serfaty, L., Montembault, S., Rosmor-duc, O., Poupon, R. Primary biliary cirrhosis - Autoimmune hepatitis overlap syndrome clinical features and response to therapy. Hepatology 1998 28 296-301... 

Duclos-Vallee, XC., Hadengue, A., Ganne-Carrie, N., Robin, E., Degott, C., Erlinger, S. Primary biliary cirrhosis - autoimmune hepatitis overlap syndrome. Corticoresistance and effective treatment by cyclosporine A. Dig. Dis. Sci. 1995 40 1069-1073... 

Gohlke, F., Lohse, A.W., Dienes, H.P, Lohr, H., Marker-Hermann, E., Gerken, G., Meyer zum Buschenfelde, K.-H. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J. Hepatol. 1996 24 699-705... 

Gopal, S., Nagral, A., Mehta, S. Autoimmune sclerosing cholangitis an overlap syndrome in a child. Indian J. Gastroenterol. 1999 18 31-32... 

Griga, T., Tromm, A., Muller, K.M., May, B. Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases. Eur. J. Gastroenterol. Hepatol. 2000 12 559-564... 

Hatzis, G.S., Vassiliou, V.A., Delladetsima, XK. Overlap syndrome of primary sclerosing cholangitis and autoimmune hepatitis. Eur. J. Gastroenterol. Hepatol. 2001 13 203 - 206... 

Storch, WJ. So-called overlap syndromes in hepatology combinations or associations of concurrent autoimmune liver and other diseases. Cell. Mol. Biol. 2003 49 645 - 648... 

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Tab. 33.1 Differentiation of autoimmune liver diseases and their overlap syndromes (s. tab. 5.20) (s. p. 658). (AHA = anti-histone antibody anti-GOR = anti-specific nuclear antigen in HCV) (see text for other abbreviations). —/(+) = no or occasional slight increase...

Autoimmune hepatitis may be classified into three (sometimes four) types according to the different antibody specificities in conjunction with the seromarkers of viral hepatitis. Further differentiation has also been made into subtypes (la, lb and 2a, 2b), although this remains controversial. In the future, it may well be possible to derive therapeutic indications or prognostic indices from these subtypes at the moment, they offer no guidance in this respect. It is, however, remarkable that ANA, SMA and LKM 1 are not primarily detectable in 20% of patients with AIH, whereas other antibodies, such as LP/SLA and ASGPR antibodies, can often be identified. (52) In this context, a more reliable definition of overlap syndromes might therefore be useful for therapy and prognosis, (s. tab. 33.1)... 

Primary biliary cholangitis The overlap of PBC with AIH reveals positivity of AMA, ANA and ASGPR as well as lower litres of LP and SMA. In approx. 20% of cases, AMA can be found in AIH. The frequency of this overlap syndrome is 5-10% (-15%). It was first detected in a child (12-year-old girl). (34) IgG and IgM fractions are simultaneously elevated. Histological findings can comprise the criteria of both PBC and CAH. Thus two different autoimmune diseases are present, whereby prognosis is determined by the degree of severity of AIH. This provides the indication for immunosuppressive therapy, (s. tab. 33.1) (s. p. 660)... 

UDCA The administration of UDCA offers the least risk due to its relative lack of side effects or interactions. It is the therapy of choice in all overlap syndromes with PBC or PSC features and also in cases with autoimmune cholangitis phenomenology. In view of the above-mentioned positive effects on chronic and acute viral hepatitis as well as in AIH, UDCA is both pharmacologically and clinically plausible as adjuvant therapy. 

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