Page 1065 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1028 Part seven Organ-Specific Inflammatory Disease

ANA and/or SMA positivity and/or hypergammaglobulinemia; (ii)
Therapy serum AMA negativity by immunofluorescence; (iii) biochemical
The treatment of PSC includes medical and endoscopic measures and/or histological features of cholestatic and hepatocellular
as well as liver transplantation. UDCA has been investigated in injury; and (iv) exclusion of chronic viral, metabolic, or toxic
several clinical trials, with conflicting results. Overall, the available liver disease. This definition possibly includes PBC with atypical
evidence suggests that UDCA fails to induce a substantial change presentation, small-duct PSC, idiopathic adulthood ductopenia,
in the course of PSC, despite remaining the most prescribed AIH with bile duct damage, concurrent AIH and small-duct
drug. However, it appears that high-dose UDCA (20 mg/kg/day) PSC, and various transitional stages of the classic diseases.
might reduce the rate of progression and possibly prevent the Consensus is awaited on this issue, and standardization of
development of colon cancer in patients with PSC and Ulcerative diagnostic criteria for overlap syndromes also has not been
colitis (UC). Endoscopic measures are indicated to treat com- achieved.
plicated PSC through the opening of short- and long-segment
stenosis of the common bile duct and short-segment stenosis OVERLAP SYNDROMES
of the hepatic ducts near to the bifurcation. The treatment can
be repeated over time once restenosis ensues, and resulting survival As many as 18% of patients with autoimmune liver disease also
rates are higher than those of patients not treated endoscopically. present with features of a second autoimmune liver disease. An
Finally, PSC represents an important indication for liver trans- even higher percentage of patients has an additional autoimmune
plantation since patients are commonly younger than those with disease, e.g., rheumatoid arthritis, Sjögren syndrome, or systemic
other autoimmune liver diseases. Recurrence of disease is common sclerosis. These patients are considered to have overlap syndromes.
and affects 20–40% of transplanted patients during prolonged Patients with hepatobiliary overlap syndromes usually present
follow-up. It is still debated whether medical treatment with with both hepatocellular and cholangiocellular injury with
UDCA in fact produces a longer survival. biochemical and histological features of AIH and PBC or PSC.
When not treated, these patients show a progressive course toward
liver cirrhosis and failure. More specifically, AIH–PBC overlap
syndrome is found in 10% of adults with AIH or PBC, and
KeY COnCePts AIH–PSC overlap syndromes are found in 6–8% of children,
adolescents, and young adults with AIH or PSC. Besides the
• Primary sclerosing cholangitis (PSC) is a chronic autoimmune cholestatic existence of overlaps, in rare cases transitions are also possible
disease that can affect all tracts of the biliary tree, including the
extrahepatic bile ducts. from PBC to AIH, from AIH to PBC, or from AIH to PSC. The
• Unlike other patients with autoimmune diseases, the majority are pathogenesis of the overlap syndromes is poorly understood,
male. and few data are available regarding the clinical characteristics
• PSC can be complicated by cholangiocarcinoma. and outcomes of such patients. Thus the clinical management
of overlap syndromes is based on single diseases, and medical
treatment remains empiric. Thus UDCA is used for chronic
cholestasis, and immunosuppressants (steroids and azathioprine)
CLInICaL PearLs are used for AIH; for end-stage disease, liver transplantation is
indicated.
• Primary sclerosing cholangitis (PSC) is frequently associated with IBD
(60–80% of patients). IgG4-RELATED CHOLANGITIS
• PSC is not associated with any specific autoantibodies; however,
perinuclear antineutrophil cytoplasmic antibodies (pANCA) may be There have been numerous reports of a new clinical entity coined
positive. autoimmune pancreatitis/IgG4-associated sclerosing cholangitis
• Imaging is helpful in detecting PSC, which manifests with strictured with peculiar clinical and therapeutic characteristics. IgG4-related
and dilated bile ducts, both intra- and extrahepatic.
sclerosing cholangitis is more frequent in men than in women,
and usually at an older age. The clinical features of the disease
appear similar to those with CCA or PSC. IgG4-related sclerosing
cholangitis has been associated with autoimmune pancreatitis,
tHeraPeUtIC PrInCIPLes and the coexistence of both manifestations is suggestive of IgG4-
related disease. The differential diagnosis with PSC may be
• Ursodeoxycholic acid (UDCA) (20 mg/kg) may be effective in slowing difficult; however, elevated IgG4 serum concentration (up to
primary sclerosing cholangitis (PSC) progression.
• Endoscopic procedures are indicated to treat stenoses. 10% of PSC patients may have elevated levels) and longer stenosis
• Liver transplantation is highly effective, and PSC represents an important found by imaging may support the diagnosis. Histology is
indication for such procedure, particularly due to the younger age of important, as it may discover an IgG4-positive lymphoplasmacytic
affected patients. tissue infiltrate. Overall, the prognosis is considered to be good;
however, some cases of portal hypertension and liver cirrhosis
have been reported.
Corticosteroids induce a remarkable improvement in clinical
AUTOIMMUNE CHOLANGITIS and biochemical manifestations, and a dosage of 0.6 mg/kg/day
of prednisolone should be started for 2–4 weeks and gradually
The term autoimmune cholangitis was first introduced to indicate tapered over 2–3 months. Immunosuppressant agents have been
AMA-negative PBC, possibly with serum ANA. However, more used effectively in anecdotal cases. The optimal treatment is still
recently this category has been expanded to include (i) serum debated.