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2. 28 /Female / Edakkalathur, Thrissur dt. Fever – 6 months Multiple swellings over the body- 6 months Yellowish discoloration of eyes and urine- 2 months.

3. Fever- Associated with chills/ rigor 4-5 days/ week Present through out the day Generalized body pain. No cough with expectoration/ burning micturition/loose stools/joint pains.

4. Multiple skin lesions over the thigh, arms and trunk- 6 months. Painful, red, warmth Spontaneous resolution. No itching/ No ulceration Yellowish discolouration of eyes and urine- 2 months. Loss of appetite+ Loss of weight- 7-8 kgs in 5 months.

5. Past history: DECEMBER 2005- FEBRUARY 2006: Fever with urticarial rash 2 months duration, admitted and evaluated at Amala hospital, Thrissur ESR: 40mm/hr, Mantoux- Negative ANA- negative USG Abdomen: B/L PCOD, Ovarian cyst Skin biopsy: Lobular Panniculitis Treated with antibiotics and Dapsone. Fever and skin lesions persisted.

6. MARCH 2006 to MAY 2006 Jubilee Mission Hospital Raised ESR (50mm/hr), Elevated ADA, LE cell, AntidsDNA, ANA : Negative ASO, RA Factor: Negative C3, C4- Normal HIV, VDRL- Negative TB IgM – positive Started on ATT; Wysolone. Took ATT for 2-3 weeks only. since her fever did not subside; and the skin lesion worsened, ATT was stopped.

7. June 2006 LISSY HOSPITAL- Ernakulam Fever with loss of appetite Non healing ulcer left gluteal region Icterus+, Raised Liver Enzymes. ANA- Negative Blood culture: Sterile Pus culture: Pseudomonas, Klebsiella Treated with antibiotics, steroids, Thalidomide.

8. Continued Wysolone for a year, tapered and stopped in June 2007. Asymptomatic for a long period till November 2008 when she developed fever again followed by skin lesions. Started on high dose Wysolone (40mg/day) No response; found to have raised liver enzymes in March 2009, came to AIMS.

9. Summary

10. Examination Conscious, oriented, febrile. Pulse: 80/min BP: 130/80mmHg RR:18/min Icterus+ No cyanosis/clubbing/LNE/Oedema NO KF ring

11. GI system: Oral cavity: N Abdomen: Soft, Liver palpable, Non tender, 4 cm below costal margin, Firm, surface smooth. No splenomegaly Shifting dullness + Chest: B/L air entry equal, normal vescicular breath sounds CVS:S1 S2 heard normally, No murmurs NS: No focal neurological deficits; No neck stiffness. Fundus: Left: Normal; Right: Medullated nerve fibres.

12. Possibilites considered were: Erythema nodosum- ? Tubercular ? Sarcoidosis Weber Christian Disease Hepatic involvement of a systemic disease. ? Auto immune ? TB ? Sarcoidosis

13. TC: 3,620 N: 81%, L: 15%, M7%. Hb: 14.6% Platelets: 2,41,000 ESR: 14mm/hr Creatinine: 0.78 T Bil:6.2mg/dl, D: 3.9mg/dl SGOT: 357IU/L, SGPT: 241.4IU/L, ALP: 418.4 IU/L Albumin: 2.8g/dl, Globulin: 3.4g/dl Na: 135.4, K:4.1, Ca: 7.9 INR: 0.99 Serum LDH: 745

14. USG abdomen: Liver enlarged, Increased echotexture. Dilated portal vein; measures 14 mm Spleen enlarged ;11cm. Moderate ascitis Pancreas, Gall bladder, Kidneys, Bladder, Uterus Normal CXR P/A: Normal

15. Ascitic fluid study: Total cells: 524/uL Lymphocytes: 90%, Neutrophils: 4%. Glucose: 166mg/dl Protein: 4.6g/dl Albumin: 2.0g/dl ADA: 50 SAAG: 0.8 Gram stain, AFB stain, Fungal stain: Negative Ascitic fluid culture: No growth. Cytopathology: Lymphocyte rich fluid. No atypical cells

16. AntidsDNA: Negative Anti SM antibody: Negative. HIV, HBV, HCV: Negative Mantoux: Negative.

17. Skin biopsy: Unremarkable dermis and epidermis. Subcutaneous tissue shows septal panniculitis with granuloma.

18. Started on second line ATT, Liver biopsy planned. Serum ACE, GGT levels Deferred due to increase in INR during hospital stay. Fever subsided with ATT, INR normalised with fresh frozen plasma

19. Patient requested discharge due to personal reasons, planned to get admitted next week for the biopsy. Diagnosis: Erythema nodosum- Septal panniculitis (TB/ Sarcoidosis) Hepatocellular jaundice with ascitis (probably TB) To r/o autoimmune causes/ sarcoidosis.

20. Erythema nodosum, a painful disorder of the subcutaneous fat, is the most common type of panniculitis. First sign of a systemic disease such as tuberculosis, bacterial or deep fungal infection, sarcoidosis, inflammatory bowel disease, or cancer.

22. Hallmark is tender, erythematous, subcutaneous nodules that typically are located symmetrically on the anterior surface of the lower extremities. Erythema nodosum does not ulcerate and usually resolves without atrophy or scarring. Represents an inflammatory process involving the septa between subcutaneous fat lobules, with an absence of vasculitis and the presence of radial granulomas.

23. Idiopathic Bacterial - Streptococcal infections, tuberculosis, Leprosy,Campylobacter, salmonella, Shigella, Gonorrhea Sarcoidosis Drugs - Sulfonamides, oral contraceptives, Amoxycillin Pregnancy

24. Deep fungal - dermatophytes, coccidioidomycosis, histoplasmosis, blastomycosis Viral/chlamydial - infectious mononucleosis, lymphogranuloma venereum, paravaccinia Enteropathies - ulcerative colitis, Crohn's disease Malignancies - lymphoma/leukemia, sarcoma, post radiation therapy

25. Tuberculosis and Liver Usually in miliary TB Localised liver TB is rare Tuberculomas, Ascitis, Cholangitis, Abscess, Porta hepatis adenopathy. Jaundice is rare. Biliary obstruction by nodes. Dispropotionate elevation of ALP Hyponatremia Marginal elevation of aminotransferases, Reversal of AG ratio A caeseating granuloma in liver biopsy.

26. Sarcoidosis and Liver Most cases remain asymptomatic Not associated with jaundice or PHTN In a small subset, chronic intrahepatic cholestasis and /or portal hypertension can complicate the course of the disease. Jaundice, Hepatosplenomegaly and pruritis ALP and GGT are very high Raised ACE levels Definite diagnosis: Liver biopsy. A caeseating granuloma rules out Sarcoidosis.

27. Collagen Vascular Disease and Liver PAN, Takayasu Polymyalgia rheumatica Cryoglobulinemia Weber Christian Disease RA Felty’s Syndrome a and b globulins elevated, Bil, SGOT/SGPT/ ALP: Normal or mildly elevated

28. Autoimmune chronic hepatitis Immunological factors causing liver injury Elevated globulins Elevated enzymes, High IgG ANA, Anti SM antibody Anti LKM antibody RA factor positivity Definite diagnosis: Liver biopsy – Inflammation characterised by mononuclear cells and plasma cells.

29. Erythema Nodosum- Management Treatment of any underlying disorders and supportive therapy, including bed rest and avoidance of contact irritation of affected areas. Pain can be managed conservatively with nonsteroidal anti-inflammatory drugs (NSAIDs). Oral potassium iodide prepared as a supersaturated solution in a dosage of 400 to 900 mg per day for one month is a therapeutic option.

30. Oral prednisone at a dosage of 60 mg (1 mg per kg body weight per day) every morning is advised. Steroids used in combination with hydroxychloroquine cyclosporin A or thalidomide have been used to treat inflammatory bowel disease–associated erythema nodosum. NSAIDs should be avoided in treating erythema nodosum secondary to Crohn’s disease because they may trigger a flare-up or worsen an ongoing acute bout.

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