Sarcoidosis is a multisystem granulomatous disease of unknown etiology

Goal: find out what is UNIQUE about this case?

a. What’s unique?

Hepatic sarcoidosis.
We describe six cases of hepatic sarcoidosis. Clinical presentation was with weight loss,
hepatomegaly and abnormal liver function tests. In addition there was fever, itching, splenomegaly
and abdominal lymphadenopathy in some. CT scan revealed mediastinal lymphadenopathy in all.
Liver biopsy showed noncaseating epithelioid granulomas. Serum angiotensin converting enzyme
was elevated in four cases. All patients had received anti-tuberculosis treatment with clinical
diagnosis of hepatic tuberculosis. None of them improved, while some showed clinical deterioration.
All patients responded to corticosteroids with disappearance of symptoms and normalization of liver
function tests.
PMID:
https://www.ncbi.nlm.nih.gov/pubmed/12839382

[SIMILAR to this case: CT: Mediastinal Lymphadenopathy, Liver: Noncaseating granuloma, Given steroid]

UNIQUE?

Isolated hepatic sarcoidosis.

Although hepatic granulomas occur in 50-65% of patients with systemic sarcoidosis, isolated liver
sarcoidosis is rare. Clinical presentation varies from asymptomatic to manifest. The diagnosis is based on
a characteristic histopathological finding of liver biopsy.

CASE REPORT:
We reported a 69-year old man was admitted due to abdominal swelling and
abdominal pain. Laboratory studies detected: cholestasis, pancytopenia and
elevaton of angiotensin-converting enzyme. Abdominal imaging techniques showed
liver cirrhosis, splenomegaly and ascites. The diagnosis of the hepatic sarcoidosis
was confirmed by histopathological examination of liver biopsy. The patient was
treated with corticosteroids. After 18 months the patient was without any subjective
symptoms, and with biochemical and clinical improvement.
CONCLUSION:
Isolated hepatic sarcoidosis should be considered in the differential diagnosis of
asymptomatic or simptomatic patients with hepatosplenomegaly and changes in
liver functional tests. Only the timely diagnosis and proper treatment can lead to
subjective and objective improvement of patients.
https://www.ncbi.nlm.nih.gov/pubmed/24783422
 b. What’s similar?

Establishing a definitive diagnosis of GI sarcoidosis depends on three components:

●Biopsy evidence of noncaseating granulomas in the "symptomatic or incident organ"
●Exclusion of other causes of granulomatous disease, particularly mycobacterial, fungal, and
parasitic infections
●Clinical, radiographic, and optimally histopathologic evidence of sarcoidosis in at least one other
organ system
When sarcoidosis is suspected but not previously diagnosed, an evaluation for evidence of extra-
intestinal involvement should be under-taken.
https://www.uptodate.com/contents/gastrointestinal-and-hepatic-
sarcoidosis?source=contentShare&csi=d8f25778-2292-4db7-8a9d-5e1146c6cec0

HEPATIC — The liver is involved in the majority of patients with sarcoidosis, although the clinical
consequences of the involvement are variable [23,62-64]. Approximately, 50 to 65 percent of
patients with sarcoidosis have granulomas on liver biopsy, but symptomatic hepatic sarcoid
occurs in 5 to 15 percent [63,65,66]. Hepatic sarcoidosis is approximately twice as common in
African-Americans as Caucasians [64,65,67]

Most patients with hepatic sarcoid are asymptomatic and have only biochemical abnormalities
(usually an elevated alkaline phosphatase and gamma glutamyl transpeptidase). Abdominal pain
and pruritus are noted in approximately 15 percent of affected patients, and hepatomegaly in 5 to
15 percent [65,67]. Fever, weight loss, and jaundice are present in less than 5 percent [67]. Rare
patients develop cirrhosis (6 percent), cholestatic liver disease with diffuse intrahepatic biliary
strictures resembling sclerosing cholangitis, obstructive jaundice due to hepatic hilar
lymphadenopathy, or hepatic vein thrombosis [13,65,67-76]. Portal hypertension, estimated to
occur in 3 percent of patients with hepatic sarcoidosis, may develop as a result of biliary fibrosis
or cirrhosis, or rarely due to periportal granulomas that restrict portal flow [62,65,67].

Among patients with clinical evidence of hepatic sarcoidosis, serum aminotransferases are
increased in 50 to 70 percent, although the degree of increase is less than the serum alkaline
phosphatase [65,67]. Hyperbilirubinemia and hypoalbuminemia are rare and associated with
cirrhosis. The serum angiotensin converting enzyme level may be elevated, but is normal in
approximately 25 percent of untreated patients, and is not useful diagnostically [77].
(See "Clinical manifestations and diagnosis of pulmonary sarcoidosis", section on 'Serum
markers'.)

Asymptomatic hepatic lesions may be first identified on the liver images of thoracic computed tomography
(CT). On contrast-enhanced abdominal CT, the typical findings are hepatomegaly and numerous
hypodense nodular lesions ranging in size from 1 mm to 3 cm (image 1) [78,79]. On magnetic resonance
imaging, T1-weighted images show hypointense nodular lesions, while on T2-weighted images the
nodules are hyperintense relative to the surrounding liver parenchyma [80]. Lesions tend to be located
around the portal veins.

Liver biopsy is recommended for patients with moderate or severe liver-test abnormalities (eg, more than
three times the upper limit of normal) [81]. Typically, the majority of biopsy specimens greater than 2 cm
in length will have noncaseating granulomas that are often located along the portal tract. As conditions
other than sarcoidosis can cause granulomatous lesions in the liver (eg, tuberculosis, fungal infections,
brucellosis, Q fever, primary biliary cholangitis, Hodgkin disease, drug toxicity), additional steps are
needed to make a confident diagnosis of sarcoidosis. These steps include identifying characteristic
extrahepatic manifestations of sarcoidosis (eg, cutaneous manifestations and/or chest imaging
abnormalities), characterization of the granulomas within the liver (location and appearance), examination
of special stains/culturesfor infectious organisms, and exclusion of malignancy and drug-induced
granulomas. (See "Hepatic granulomas", section on 'Differential diagnosis'.)

c. What’s been recorded in the past?

d. What’s the teaching point?

What is Peritoneal Sarcoid?

PERITONEAL — Peritoneal involvement is an uncommon manifestation of sarcoidosis, especially in the

absence of splenic, hepatic, adnexal, or small intestinal involvement [82]. Patients usually complain of
abdominal pain. Ascitic fluid is typically identified by computed tomography or peritoneal studding and
ascites are noted at the time of laparoscopy. The peritoneal fluid is usually a lymphocyte predominant,
low serum-ascites albumin gradient fluid (ie, SAAG <1.1 g/dL) [83]. In contrast, when sarcoidosis causes
ascites due to cor pulmonale or portal hypertension, the fluid has a high serum-ascites albumin gradient
(ie, SAAG ≥1.1 g/dL). (See "Evaluation of adults with ascites", section on 'Serum-to-ascites albumin
gradient'.)

https://www.uptodate.com/contents/gastrointestinal-and-hepatic-
sarcoidosis?source=contentShare&csi=d8f25778-2292-4db7-8a9d-5e1146c6cec0

e. Teaching point?
f. What made him think this was Sarcoid?
i. Patient had a LOW SAAG

WHICH Dz have low SAAG?

WHICH Dz have HIGH SAAG

2. Which disease has HIGH TOTAL PROTEIN?

3. When patient has High Total Protein in ascites patient…….what does this mean?
4. Low SAAG, High protein….Sarcoidosis
a. What percent of SARCOIDOSIS has LOW SAAG, High Protein?

AFTER DISCOVERED
 What are possible Treatment?
 o Steroid? Within how many months? (for it to be reversible) can reverse the changes…pt
can return to normal living/quality of life

TREATMENT — The decision to treat gastrointestinal (GI) sarcoidosis is based upon the activity and
extent of disease. Asymptomatic patients generally do not require treatment. For patients who are
symptomatic and have a substantial amount of granulomatous inflammation on tissue biopsy,
glucocorticoids are the treatment of choice, based on extrapolation from the treatment of pulmonary
sarcoidosis [23].

Hepatic sarcoid ─ An optimal therapeutic regimen for hepatic sarcoidosis remains ill-defined. It has
been proposed that patients with symptomatic hepatic sarcoidosis receive prednisone, following the
above approach. This includes patients with diffuse intrahepatic biliary strictures due to sarcoid [81].
In a series of 63 patients with hepatic sarcoid treated with prednisone, approximately one-third had
a complete clinical response, one-third a partial response, and one-third no response [85]. Even in
patients with advanced disease (ie, portal hypertension or cirrhosis), our practice is to try an initial
course of prednisone. (See "Hepatic granulomas", section on 'Sarcoidosis' and "Treatment of
pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy".)

Of alternative agents used in hepatic sarcoidosis, methotrexate deserves special mention [86].
Despite the potential risk of hepatic toxicity, methotrexate has been shown to reduce abnormal liver
function test abnormalities and to be glucocorticoid sparing in this setting [65,85,87].
(See "Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy".)

Although hepatic involvement is common, end-stage liver disease and other hepatic complications
were rare indications for orthotopic liver transplantation (OLT) in the United States from October
1987 to December 2007 and accounted for only 0.12 percent of OLT recipients [88]. The one and
five-year survival rates of the 102 patients that were transplanted for hepatic sarcoidosis were 78
and 61 percent respectively [88]. Sarcoidosis can recur in the transplanted liver [88-91].
Interventions for other hepatic complications may include:
•Liver transplantation for the rare occurrence of hepatic vein thrombosis due to compression of
the hepatic veins by sarcoid granulomas [68-70]. (See "Budd-Chiari syndrome: Epidemiology,
clinical manifestations, and diagnosis".)
•Treatment for portal hypertension (presumably presinusoidal due to the presence of periportal
granulomas), which is similar to that for portal hypertension of other etiologies and includes
liver transplantation [65,92,93]. (See "Portal hypertension in adults".)
•Ursodeoxycholic acid may be of benefit for patients with a syndrome of intrahepatic
cholestatic jaundice with pruritus and hypercholesterolemia resembling primary biliary
cholangitis [81,94,95].

https://www.uptodate.com/contents/gastrointestinal-and-hepatic-
sarcoidosis?source=contentShare&csi=d8f25778-2292-4db7-8a9d-5e1146c6cec0

The liver is almost always involved in patients with gastrointestinal sarcoidosis, but may be affected in the
absence of other gastrointestinal involvement. Symptomatic hepatic sarcoidosis is less common. The
differential diagnosis of granulomatous hepatitis is broad, and the diagnosis and treatment of hepatic
sarcoidosis are discussed separately. (See 'Hepatic' above and "Hepatic granulomas", section on
'Sarcoidosis'.)

TREATMENT:

Observation without medical management

Observation alone is indicated for patients with asymptomatic liver disease or mild elevations of
serum liver enzymes, and normal synthetic liver function without evidence of
cholestasis.17,19,49 Hepatomegaly alone noted on physical examination and/or radiographic
investigation in the absence of symptoms does not qualify as an indication for treatment. It has
been noted that in some asymptomatic patients, abnormal serum liver tests can resolve
spontaneously or remain stable for many years.25,34
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Medical treatment
For patients who have symptoms of liver involvement, and have biochemical evidence of
cholestasis or who are at high risk for developing hepatic complications, pharmacological
therapy should be considered.17,19,49 The first line agents that have been studied include
corticosteroids and ursodeoxycholic acid.
Go to:

Steroids
It has been shown that corticosteroids can decrease the number of hepatic granulomas by
suppression of the inflammatory response,50 and reduce liver size25 which may be helpful for
patients with persistent abdominal pain due to hepatomegaly. In addition, steroids are
recommended for patients with constitutional symptoms such as fever, fatigue, pruritus, and
weight loss. Low-dose prednisone (10–20 mg/daily) may be sufficient for those with mild
symptoms, while a higher dose of prednisone (20–40 mg/daily) is warranted for those with
severe symptoms.17,51 Prednisone can also be considered for patients with significant
adenopathy in the porta hepatis.
Treatment duration should be determined by clinical and laboratory response. Some authors
recommend 12 months of therapy before tapering the dose.52 Relapsing symptoms may require
long-term therapy or steroid-sparing agents. Side effects of long-term steroid use (including
ostopenia, bone fractures, avascular hip necrosis, hyperglycemia, cataracts, and hypertension)
should be considered.52 No studies have reported on the use of oral budesonide (a systemic
steroid eliminated on first pass through the liver) in the treatment of hepatic sarcoidosis.
The benefit of steroids in patients at the extremes of the clinical spectrum (that is, asymptomatic
individuals or patients with cirrhosis and portal hypertension) is questionable. Steroids can help
in the normalization of these laboratory abnormalities in asymptomatic patients with elevated
aminotransferases.14,34 However, it is important to consider that serum liver tests can normalize
spontaneously.25,34 Because there is a lack of long-term studies, it is unclear if steroids prevent
liver damage or halt the progression of the disease. In patients with progressive disease
(significant fibrosis, chronic cholestasis, and portal hypertension), steroid treatment has not been
shown to have beneficial effects.16

Second-line and third-line agents

These agents may be useful for patients for whom prednisone fails or patients who are deemed to
be steroid dependent. Azathioprine has been reported to normalize aminotransferases, but can
also cause acute hepatitis.49 Methotrexate, glutathione, chlorambucil, cyclosporine,
cyclophosphamide, thalidomide, pentoxifylline, and infliximab56,57 have been reported to be
beneficial. However, there is inadequate evidence to support the use of these agents.49
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Treatment of advanced liver disease

Portal hypertension and decompensated cirrhosis should be managed by standard measures.
Steroids may not be beneficial, and liver transplantation may be required. Reported rates of graft
and patient survival for hepatic sarcoidosis are 78% at 1 year, 66–67% at 3 years, and 60–61% at
5 years.29 Recurrence of disease in the graft has been reported.58

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521279/