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Hepatic tuberculosis presenting with extreme hyperferritinemia masquerading as adult-onset Still’s disease: a case report
© Manoj et al.; licensee BioMed Central Ltd. 2012
Received: 26 December 2011
Accepted: 12 July 2012
Published: 12 July 2012
Isolated hepatic tuberculosis is an uncommon manifestation of one of the most common infections worldwide, caused by Mycobacterium tuberculosis. Extremely high serum ferritin, which is regarded as a marker of adult onset Still’s disease, has not been observed in patients with tuberculosis of the liver. We report a case of hepatic tuberculosis who presented with clinical criteria of adult-onset Still’s disease and extreme hyperferritinemia, which posed a diagnostic confusion.
Our patient was a 48-year-old Sri Lankan man who presented with fever, polyarthralgia and a generalized skin rash of three months duration. He had marked constitutional symptoms, oral ulcers, hair loss, anemia and hepatomegaly. Laboratory investigations disclosed an inflammatory syndrome, evidence of hepatic dysfunction, bone marrow suppression and a raised serum ferritin level of 34,674 ng/ml. A rapidly deteriorating course of illness prompted treatment based on a presumptive diagnosis of adult-onset Still’s disease until liver histology was available. The patient died of sepsis followed by multi-organ dysfunction. Later, the liver histology revealed tuberculosis.
Extrapulmonary tuberculosis, although well known to present with peculiar manifestations, has not been reported to be associated with extremely high levels of serum ferritin in immunocompetent individuals. Isolated hepatic tuberculosis presenting with clinical criteria of adult-onset Still’s disease is remarkable. Since tuberculosis remains a potentially curable disease, an awareness of its’ protean manifestations is essential.
Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of uncertain etiology. Several micro-organisms, especially viruses, have been postulated in the pathogenesis of juvenile and AOSD . Tuberculosis (TB) is considered a common devastating infection which may affect any organ of the body giving rise to peculiar clinical presentations. Often this may lead to a considerable confusion in diagnosis unless there is a strong suspicion of mycobacterial infection. Although TB affecting the liver is not a rare entity, isolated hepatic TB presenting as fever, skin rash and joint pains with extremely high serum ferritin is remarkable. To the best of our knowledge, hepatic TB presenting with clinical criteria of AOSD has not been reported previously.
We report the case of a 48-year-old Sri Lankan man who was admitted to our facility with an intermittent fever associated with joint pains and a skin rash for three months. He had an inflammatory type symmetrical arthralgia confined to large joints with early morning stiffness for 30 minutes. Skin rash, which was non-itchy, non-scaly and non-photosensitive, appeared initially on the trunk but became generalized within a period of two weeks. He was overwhelmed with marked malaise, severe anorexia, weight loss of 19 kg over three months with significant hair loss and multiple painful oral ulcers. He had a watery diarrhea of three to four bowel movements a day of one month duration associated with occasional episodes of vomiting and a vague abdominal pain. His past medical history was unremarkable except for two uncomplicated episodes of malaria about twenty years previously. He denied either exposure to high risk sexual activities or intravenous drug use. He did not consume alcohol and was a non-smoker.
His dyspnea and tachypnea, attributable to bronchospasm associated with systemic inflammatory reaction (SIRS) was probably worsened by high fever, marked myalgia, right hypochondrial tenderness with enlarged liver and anemia. Considering the possibility of sepsis, broad spectrum antibiotic treatment with intravenous meropenem 1g daily and metronidazole 500mg every eight hourly was instituted from the day of admission. His symptomatology and respiratory distress was only slightly improved with bed rest in a propped up position, antipyretics, salbutamol nebulization, analgesics and blood transfusions to correct the anemia. He underwent liver biopsy on day two of admission after the correction of clotting abnormalities.
Fever ≥39°C (one week or longer)
Arthralgia and/or arthritis (two weeks or longer)
Non-pruritic, pink, macular or maculopapular rash, usually during febrile episodes (evanescent, salmon-pink rash)
Leucocytosis (>10,000mmol/L, >80% neutrophils)
Lymphadenopathy and/or splenomegaly
Liver involvement (raised serum transaminases and/or lactate dehydrogenase)
Negative rheumatoid factors and antinuclear antibodies
We describe the case of a previously immunocompetent man presenting with clinical criteria of AOSD with extremely high serum ferritin, secondary to hepatic TB. In extra pulmonary TB, hepatic involvement has been regarded as uncommon but not an exceptional manifestation . Most of the cases usually occur in association with milliary TB, mainly acquired through hematogenous dissemination. Our patient did not have convincing evidence of pulmonary or direct bone marrow involvement to suggest disseminated TB. Ultrasound examination and computed tomography (CT) findings have a low specificity in the diagnosis of liver involvement in TB .
Literature review of cases with extremely high serum ferritin
WBC 5800/ mm3
HIV with milliary TB
WBC 2400/ mm3
Acute hepatic damage
Iron: 12umol/L Tr.: 40%
Post-operative Hepatic ischemia
Iron: 49 umol/L Tr. : 79%
ALT;1790IU/L Iron 26 umol/L Tr.t: 45%
Post-operative hepatic ischemia
ALT : 2510IU/L
Dissection of coronary arteries and hypotension
PUO Hepatosplenomegaly Pleural effusion Rash;erythema-multiform
Leucocytosis DIC Hemophagositic-syndrome
Breast carcinoma Paraneoplastic syndrome
Evolving bone marrow hypoplasia and granulomatous hepatitis can both sometimes be associated with AOSD. Bone marrow involvement in AOSD is explained as hemophagocytic syndrome and is considered a poor prognostic sign . Hemophagocytic syndrome, defined as phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues, is an unspecific phenomenon found in several conditions such as hemolytic anemia, malignant disease and infections. In our patient, although bone marrow hypoplasia was present, convincing evidence for hemophagocytic syndrome was not seen.
The liver biochemistry of our patient can be interpreted as infiltrative disease favoring granulomatous hepatitis. Granulomatous hepatitis can be associated with autoimmune or rheumatological conditions, malignancies, systemic infections or drugs, but the most common cause is TB . However, if a patient presents more atypically, as did our patient, clinicians may initially not suspect TB as the diagnosis. Absolute exclusion of TB is a huge challenge in a resource limited setting such as Sri Lanka. The variable sensitivity and reliability of certain tests, such as tuberculin skin test, sputum for acid-fast bacillus acid-fast bacillus (AFB), TB-polymerase chain reaction (PCR), and so on. is a considerable barrier to confident early exclusion of TB. In our case, the decision making process was further compromised by the late presentation of our patient and the considerably long time needed for the gold standard test, M. tuberculosis culture to confidently exclude TB.
Unfortunately, our patient, who presented late in the course of deteriorating illness, prompted us to make an early therapeutic decision to entertain the presumptive diagnosis of AOSD. A trial of anti-tuberculous therapy (ATT) was precluded by well known liver and bone marrow toxicity effects of ATT in a patient with already impaired hepatic and hematopoetic functions in the background of a lack of solid evidence of TB. The retrospective analysis of this case would justify a trial of ATT or to combine ATT with parenteral steroids in our patient considering the dramatic consequences. Delayed histological diagnosis due to late presentation, atypical manifestations, poor prognostic features such as bone marrow involvement and immunosuppression with corticosteroids would eventually have accelerated the deterioration of his condition.
This patient gives us a caution that exclusion of TB is a high priority in differentiating causes of possible granulomatous liver disease. This step is pivotal, especially when the immunosuppressive therapy is proposed for patients living in a country that is hyperendemic for M. tuberculosis. On the other hand, this is probably the first reported case of hepatic TB presenting with extremely high serum ferritin levels and clinical criteria of AOSD. Since TB remains a potentially curable disease, an awareness of its protean manifestations is essential.
Written informed consent was obtained from the patient’s next-of-kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Dr. Janakie Fernando, consultant histopathologist of National Hospital of Sri Lanka for arranging histological examination of the liver biopsy. Dr N.D. Vidanapathirana for assisting in making corrections of the manuscript.
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