Hepatic Granulomas - Case Study Example

Table of Contents I. Introduction ……………………………………………………………….. 3 II. Pathophysiology …………………………...…………………………….. 3 III. Aetiology or Etiology …………………...………………………………… 4 IV. Pathogenesis ……………………………...……………………………… 6 V. Pathology ……………………………...………………………………….. 7 VI. Diagnosis …………………………………………………………………. 8 VII. Treatment ………………………………………………………………….. 9 VIII. Clinical Features …………………………………………………………… 9 IX. Imaging Studies …………………………………………………………… 10 X. Clinical Intervention ………………………………………………………. 10 XI. Conclusion …………………………………………………………………. 11 Appendix I – List of Drugs that Causes Granulomas …………………………. 12 Appendix II – List of Complete Etiologies of Granulomas …………………… 13 References ……………………………………………………………………….. 14 - 17 Introduction ‘Hepatic granulomas’ is a medical term used to refer to abnormal small clumps that build up on cells whenever certain physical health disorder such as tuberculosis, schistosomiasis, sarcoidosis occurs. (Herrine, 2007) As stated by Sneller (2002), a granuloma is “any nodular organized aggregation of mononuclear inflammatory cells or collection of modified macrophages that is normally surrounded by a rim of lymphocytes which often contains multinucleated giant cells”. As high as fifty-three percent of the patients with hepatic granulomas has been diagnosed with tuberculosis. (Tuncer et al., 2001) In line with this matter, Alcantara-Payawal et al. (1997) stated that as much as 50 to 80% of patients who are drying from tuberculosis were observed to have clinical evidence of hepatic granuloma. (Alcantara-Payawal et al., 1997) For this study, the researcher will discuss the basic pathophysiology on hepatic granulomas including its aetiology, pathogenesis, pathology, diagnosis, treatment, clinical features, imaging studies and the necessary clinical intervention on the said disease. Pathophysiology Pathophysiology is basically referring to the study of biological and/or physical manifestations of diseases that are highly correlated with physiological abnormalities. (Scanlon, 1999: 1186) A granuloma is a chronic inflammation of the macrophages, epitheloid cells as well as the giant multinucleated cells. (Williams & Williams, 1983) Normally, the formation of a granuloma occurs when there is a coordinated interaction between the monocytes and macrophages, lymphocytes, epithelioid cells, eosinophils, neutrophils and fibroblasts. (Oloris et al., 2007) As a clinical sign or a manifestation of infection, presence of toxic substances, allergic reaction, reaction of the autoimmune system, including the presence of neoplastic diseases (Williams & Williams, 1983), the formation and development of hepatic granulomas is normally induced by the presence of a foreign body tissue such as the schistosome eggs (Van de Vijver et al., 2006; Loeffler et al., 2002) or Schistosoma mansoni eggs (Oloris et al., 2007) within the presinusoidal capillaries. These eggs normally secretes antigens that could activate the growth of the endothelial cells. It is the CD4+T cells responding to the presence of the egg antigens that causes the granuloma formation starts to develop around the tissue-trapped eggs. (Van de Vijver et al., 2006; Mwinzi et al., 2004) Even though the real cause of granuloma formation remains unclear, it is believed that the lesions that occur protects the poorly soluble exogenous and/or endogenous irritants. (Hepatitis-Central, 2008) In other words, the body’s immunologic mechanisms converts the mononuclear phagocytic cells into epithelioid cells to form the granulomas. Aetiology or Etiology Aetiology, also known as etiology, is referring to the study of disease’s causation. The common causes of hepatic granulomas can be induced by the use of pharmacological drugs such as allopurinol, phenylbutazone, quinidine, and sulphonamides among others. (Bonilla et al., 2006; Pichardo-Bahena & Méndez-Sánchez, 2002; Tuncer et al., 2001) (See Appendix I – List of Drugs that Causes Granulomas on page ) Hepatic granulomas may also occur due to systemic disorders caused by bacterial infections such as in the case of tuberculosis, brucellosis, tularaemia, actinomycrosis, cat-scratch fever, Q fever, syphilis, and/or other mycobacterial infections. (Pichardo-Bahena & Méndez-Sánchez, 2002; Williams & Williams, 1983) In line with the presence of mycobacterial infection, it is believed that the main stimulus of necrosis is caused by the formation of immune complexes between the excess antigen and antibodies which usually occurs within the area of lesion. (Spector, Marianayagam, & Ridley, 1982) Based on the experimental study that was conducted by Ridley, Marianayagam, & Spector (1982), as soon as the strength of the cell-mediated immunity declines, mycrobacteria starts to reproduce without the control of the macrophage. On the other hand, in case the cell-mediated immunity regain its strength, the number of bacteria the grows within the area will start to decline causing the immune complexes to form anti-body excess which results in the formation of epithelioid granuloma rather than the typical necrosis. (Spector & Heesom, 1969) In rare cases, these infections can be triggered by viruses, parasites, and/or fungus. Among the common fungal infections includes: histoplasmosis, cryptococcosis, and blastomycosis including parasitic infections such as schistosomiasis, toxoplasmosis, and visceral larva migrans whereas viral infections includes infectious mononucleosis and cytomegalovirus. (Bonilla et al., 2006; Pichardo-Bahena & Méndez-Sánchez, 2002; Tuncer et al., 2001) Aside from infectious diseases, Q-fever, syphilis, and cat-scratch fever; hepatic granulomas may also occur due to: sarcoidosis, Wegener’s granulomatosis, hepatitis C, Crohn’s disease, metastatic cancer, polymyalgia rheumatic, Hodgkin’s lymphoma diseases, connective tissue disorders, and other collagen-vascular diseases. (Bonilla et al., 2006; Pichardo-Bahena & Méndez-Sánchez, 2002; Sneller, 2002) (See Appendix II – List of Complete Etiologies of Granulomas on page ) Pathogenesis Pathogenesis is actually referring to the origin and the chain of development that leads to a particular disease. (Medicine Net, 2003) Pathogenesis in the formation of granulomatous is considered complex since it involves a lot of mechanisms which causes the development of inflammatory lesion needed in destroying the presence of intracellular pathogens. (Sneller, 2002) Basically, the formation of granulomas is usually caused by chemokines which gathers the macrophages in one particular area in the human body. (Katsunori et al., 2002) Occassionally, these macrophages are mixed with the other cells such as the epithelioid, mutlinucleate giant, as well as other immunocompetent cells. Based on the study that was conducted by Katsunori et al. (2002), the deficiency of the C-C chamokine receptor-2 (CCR2) significantly increases the size of heptatic granuloma formation. Given that CD-4 is deficient from MH II or DC4 gene, there is a huge possibility that the formation of granuloma will be poorly organized. (Caruso et al., 1999) In some cases, granuloma formation may also occur when a cell-mediated immune response that is totally dependent on the CD4+T cells becomes sensitive to the presence of a schistosomal egg. (Iacomini, Ricklan, & Stadecker, 1995) It only takes an estimated time frame of 8 to 10 weeks for the T cell-mediated granuloma to respond. During the acute stage, granuloma is expected to produce cytokine before the infection develops into chronic stage after 16 to 20 weeks. (Rumbley et al., 1998) Pathology Pathology is the study and diagnosis of how diseases such as infections and hepatic granuloma develop by examining the molecular, cellular and organs levels. (UNSW Medicine, 2008) The formation of hepatic granulomas usually start when a person has been infected either with infectious intracellular pathogens such as the mycobacterium tuberculosis, schistosomes, and listeria monocytogenes or non-infectious agents like berylliosis or silicosis. (Sneller, 2002) Several studies show that granulomas is composed of macrophages, T cells, and mature dendritic cells which acts as an antigen that could activate the T cells. (Krupa et al., 2002; Tsuchiya et al., 2002) In case the T cell-dependent antigens are detained by the Kupffer cells, the in and out of DC precursors that is present in the affected organ will increase. The problem with the continuous in and out of DC procursors is the fact that it has the capability to capture antigen which will mature in the affected organ. Eventually, the said antigen will enter the T cell area of the hepatic lymph nodes in order to activate and expand the CD4 T cells. (Matsunol & Ezaki, 2000) As soon as CD4 T cells is activated, it will move back to the affected organ to form granulomas. (Yoneyama et al., 2002; Matsunol & Ezaki, 2000) During the first seven days of granulomas formation, the presence of osteopontin (OPN) does not affects the formation of granulomas. However, OPN deficiency1 during the late stage of granulomas formation could lead to the decrease in the number and size of hepatic granulomas. (Morimoto et al., 2004) As a result, injury on affected organ such as liver tissue is expected to be less serious since the volume or size of macrophages, CD-4 T cells, dendritic cells, and tumor necrosis factor (TNF) – α that is produced within the affected organ will be reduced. Diagnosis Diagnosis on hepatic granulomas is usually done through liver function tests like liver biopsy. (Bonilla et al., 2006; Tuncer et al., 2001) In case the body location where hepatic is suspected to develop in bone, a bone marrow biopsy can also be used. (Bonilla et al., 2006) Based on the test result of liver and bone biopsy, physicians can tell whether or not the main causes of hepatic granulomas are treatable or not. This test can also be used in detecting evidences of the etiology such as the caseation of tuberculosis, the presence of fungal organisms, or schistosomal ova. (Hepatitis-Central, 2008) To test whether the main cause of hepatic granulomas is caused by bacteria, fungus, or other organisms, the use of acid-fast test can be utilized since this type of diagnostic test is sensitive enough to give an accurate result. (Bonilla et al., 2006) In most cases, imaging tests like computed tomography (CT) scan, MRI, or ultrasonography are used only to show the presence of calicification in case granulomas have been present for a long period of time. Other tests such as cultures, skin tests, laboratory tests, imaging tests, and other tissue specimens can be used as necessary. (Hepatitis-Central, 2008; UNSW Medicine, 2008; Bonilla et al., 2006; Tuncer et al., 2001) Treatment Hepatic granulomas can be treated based on the main causes of physical disorders. For example: when a patient with hepatic granulomas has been diagnosed with the symptoms of tuberculosis combined with a prolonged fever, the application of empiric antituberculous therapy can be considered. (Herrine, 2007; Cunha, 1996) In case the patient has been diagnosed with tuberculosis and/or other forms of infections, the use of corticosteroids drugs as treatment can be considered except when the patient has been diagnosed with sarcoidosis. (Herrine, 2007) The study of Kawashita et al. (2006) concludes that it is possible to treat patients who has been diagnosed with hepatic granulomas by applying simple observation or a conservative therapy combined with anti-inflammatory drugs such as antibiotics or steriods. Basically, the use of empirical antibiotic therapy is not effective when the patient is experiencing inflammatory reactions caused by necrotic tissue since antibiotics could only increase the development of antibiotic-resistant bacteria like Methicillin-Resistant Staphylococcus Aureus (MRSA) whereas the use of steroids can be effective in treating sarcoidosis. (Kawashita et al., 2006) The authors explained that steroids is not recommended for patients with tuberculosis since it could only increase patient’s risk of mortality. Clinical Features Among the common clinical features that can be noted with hepatic granulomas includes a minor hepatomegaly, splenomegaly, lymphadenopathy, ascites, and peripheral edema combined with a little or no jaundice at all. (Hepatitis-Central, 2008; Ibrahim et al., 2000) Sometimes, patients with hepatic granulomas may also experience symptoms such as significant weight loss, fever, anorexia, abdominal pain, night sweats, chills, malaise including other systemic symptoms of infection. (Ibrahim et al., 2000) In case a patient has been diagnosed with tuberculosis and/or fungal infections, a prolonged fever of unknown origin (FUO) can be observed. (Hepatitis-Central, 2008; Bonilla et al., 2006) Imaging Studies Aside from using a normal chest x-rays to test for possible liver-related diseases, ultrasound combined with CT scan that shows a diffused image of nodules that can be present either in the liver or spleen can also be used. (Bangroo & Singh, 2005; Goodgame & Mallat, 2001) Basically, the use of different radiologic features of imaging test enables radiologists to enlarge the image of potential abdominal lymph nodes. Clinical Intervention Aside from the use of patient’s history record, physicians normally test the common signs and symptoms of diseases that could trigger the development of hepatic granulomas. Basically, necessary medication and/or surgery would depend on the type of disease that contributes to the formation of granulomas. In line with the clinical intervention on hepatic granulomas, physicians and other health care professionals should avoid administering antibiotics to patients who have been diagnosed with Methicillin-Resistant Staphylococcus Aureus whereas steroids should never be given to patients with tuberculosis. (Kawashita et al., 2006) Conclusion Hepatic granulomas normally develop together with physical health disorder such as tuberculosis, schistosomiasis, sarcoidosis. Therefore, health care professionals should always be aware of the possibility that patients can be suffering from any of these major physical health disorders whenever the presence of hepatic granulomas has been diagnosed. *** End *** Appendix I – List of Drugs that Causes Granulomas List of Drugs that Causes Granulomas Allopurinol Alpha-methyldopa Aspirin Bacille Calmette-Guérin therapy or vaccination Barium Beryllium Carbamazepine Carbutamide Cephalexin Chlorpromazine Chlorpropamide Copper Dapsone Diazepam Diltiazem Dimethicone Disopyramida Feprazone Glibenclamide Gold sodium thiomalate Gree-lipped mussel Halogenated hydrocarbons Isoniazid Mestranol Metolazone Mineral oil Nitrofurantoin Norethyndrone Norethynofrel Norgestrel Oxacillin Oxyophenbutaz-one Oxiphenisatin Papaverine Penicillin Phenazone Phenprocoumon Phenylbutazone Polyvinyl pyrrolidone Prajmalium Procainamide Procarbazine Pronestyl Quinidine Quinine Ranitidine Silica Succinylsulfathiazole Sulfadiazine Sulfadimehoxine Sulfadoxine-pyrimethamine Sulfanilamide Sulfasalazine Sulfonamides Sulfonylurea agents Thorotrast (thorium dioxide) Tocainide Tolbutamide Trichlormethiazide Trimethroprim-sulfamethoxazole Source: Kanel G.C., Korula J.: Granulomas, in Kanel and Korula Liver Biopsy Evaluation, Philadelphia, Penn, Saunders (2000), p. 221. In Pichardo-Bahena R. and Méndez-Sánchez N. (ed) ‘Epithelioid Granulomas in a Patient with Hepatitis C Virus’ Annals of Hepatology (2002):1(2):91 – 93. Appendix II – List of Complete Etiologies of Granulomas List of Etiologies of Granulomas Actinomycosis Adenoma, liver cell Alcoholic fatty liver Ascariasis Bacterial sepsis Boutonneus fever Brucellosis Candidiasis Cat-scratch disease Chronic granulomatous disease of childhood Coccidioidomycosis Cryptococcosis Cytomegalovirus infection Drugs/toxins Eosinophilic gastroenteritis Epstein-Barr virus infection Farber’s lipogranulomatosis Fascioliasis Foreing body giant cell reaction Hepatocellular cercinoma, fibrolamellar type Histoplasmosis Hydatid cyst Idiopathic granulomatous hepatitis Inflammatory pseudotumor Langherhan’s cell histiocytosis Leishmaniasis Leprosy Leukemia, hairy cell Listeriosis Lymphoma, Hodgkin’s and non-Hodgkin’s Melioidosis Mucolipidosis II Mycobacterium avium-intracellulare infection Nocardiosis Nonalcoholic steatohepatitis (secondary to jejunoileal bypass) Nonspecific reactive hepatitis Paracoccidioidomycosis Penicilliosis Polyarteritis nodosa Primary biliary cirrhosis Q fever Rheumatoid arthritis Salmonellosis Sarcoidosis Schistosomiasis Syphilis, congenital, secondary and tertiary Systemic lupus erythematosus Toxoplasmosis Tuberculosis Visceral larva migrans Whipple’s disease Zygomycosis Source: Kanel G.C., Korula J.: Granulomas, in Kanel and Korula, Liver Biopsy Evaluation. 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