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Infectious Diseases Case Presentation 18 September 2002

Infectious Diseases Case Presentation 18 September 2002. Dr Zakeya Bukhary, Fellow, Infectious Diseases Dr Hail Al-Abdely, Consultant, Infectious Diseases. First Case. History. A 19-year-old girl from the Eastern Province, who was completely healthy until May 2001 when started to c/o:

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Infectious Diseases Case Presentation 18 September 2002

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  1. Infectious DiseasesCase Presentation18 September 2002 Dr Zakeya Bukhary, Fellow, Infectious Diseases Dr Hail Al-Abdely, Consultant, Infectious Diseases

  2. First Case

  3. History • A 19-year-old girl from the Eastern Province, who was completely healthy until May 2001 when started to c/o: • RIF pain and fever associated with constipation and weight loss • The pain was colicky and slowly progressive, moderately severe, non-radiating and not relieved by analgesics

  4. History • Fever was on and off with no diurnal variation and no night sweating or chills • No nausea or vomiting • No skin rash or joint pains • Systemic review: unremarkable

  5. History • No Hx of TB or contact with TB patients • No previous abdominal surgeries • No drug Hx • Lives in Dhahran

  6. History • At the local hospital (DHC), she was found to have ileocecal mass (5/2001) • Colonoscopy showed ulcers of the Rt hemicolon and Bx was consistent with acute inflammation. • Started empirically on ciprofloxacin + flagyl but without response

  7. History • Colonic biopsy ? Crohn’s. • Started on oral steroids. • Has temporary improvement and gained wt. • Oct 2001, f/u showed an increase in the mass size clinically and confirmed by CT abdomen.

  8. 27 Oct 2001, laparatomy (at DHC) showed unresectable mass with intense inflammation involving the Rt. hemicolon • Bx showed necrotizing granuloma with broad fungal hyphae. Culture was negative. • Treated with ABLC and continued low dose steroid • On 11 Nov 2002  referred to KFSH&RC for 2nd opinion

  9. Pt was clinically unwell but not toxic • P/E: • T 38.8ºC PR 110/min BP 120/70RR 20 Wt 49 kg Ht 158 cm • Not in distress or jaundiced or cyanosed • Was pale • No LN enlargement • Chest/heart exam  unremarkable

  10. Abd Exam • Soft, with large, irregular, ill-defined mass extending from the RUQ to RIFand umbilical region; mildly tender and hard. • Non-palpable liver or spleen • No ascitis • B.S. were present

  11. Investigation WBC 14.0 PMN 80% No bands Lymph 20.0% Eosinophils 1.3% Hb 92 MCV 78.8 MCH 23.4 Plt 305 ESR 15 Urea 4.9 Cr 96 Na 135 K+ 3.3 ALT 50 ALP 185 Bil 4 Alb30 PPD skin test –ve CXR  N

  12. CT abdomen 12 November 2001

  13. Differential Diagnosis

  14. D. Dx • Deep GI mycosis • TB • Actinomycosis • Crohn’s • Lymphoma

  15. Course • Review of histopath slides from DHC – showed moderate chronic colitis, no cryptitis with positive granuloma and fungal hyphae • With prominent eosinophilic infiltrate

  16. Pathology

  17. Pt was spiking high grade Temp 40.0º C • Started on Ambisome + Tazocin for possibility of perforation and superadded bacterial infection • Pain control, NPO, TPN • Surgical opinion confirmed that the mass was non-operable

  18. Course • 14 Nov 2001 • FNA and True cut Bx to get tissue for microbiological Dx for c/s • 17 Nov 2001 • Steroids - methylprednisone 1 mg/kg/d started

  19. Course • 20 Nov 2001 • Dx of GI mycosis confirmed by culture positive Basidiobolus ranarum • IV itraconazole was added • Ambisome changed to Ampho B to minimize drug induced hepatitis

  20. Course • f/u CT scan Abd (20/11/2001): • showed very impressive response to steroids + antifungal (Ampho B + short course of itraconazole) with regression of the inflammation and dilatation of the Rt. hemicolon which has emptied its content and has partly collapsed.

  21. Clinically, pt was improving with no fever and no abd pain • Started on oral feed • 11 Dec 2001  discharged on ketoconazole 600 mg p.o. OD, and steroids on tapering dose • In vitro - susceptibility test showed better inhibitory effect of ketoconazole which was started orally

  22. CT abdomen 8/4/2002 2/9/2002

  23. Discussion

  24. Basidiobolomycosis • Introduction • Classification • Epidemiology • Pathogenesis & Clinical Manifestation • Diagnosis • Revision of invasive G.I.B. • Rx

  25. Zygomycetes Mucorales(Mucormycosis) Entomophthorales(Entomophthoramycosis) Basidiobolus Conidiobolus

  26. Basidiobolus species are normal inhabitants of soil throughout the world • They have been also isolated from the gut of amphibians and reptiles

  27. These fungi cause a chronic inflammatory granulomatous disease (Entomophthoramycosis) • reported in healthy inhabitants of tropical and subtropical regions (Africa, Southeast Asia, South America)

  28. The mode of transmission of infection to humans remains unknown • Inhalation, ingestion, direct inoculation and acquisition secondary to I.M. injection and insect bites have been postulated

  29. The disease generally manifested as subcutaneous lesions • Visceral involvement and deep invasive infection either primary or secondary to subcutaneous disease, is rare and affects mainly immunocompromised hosts and can be fatal. Nazir et al, Ann Trop Paediatrics 1997;17:161

  30. Diagnosis depends on microscopic documentation of tissue invasion and presence of typical hyphae of B. ranarum • In contrast with mucormycosis no vascular invasion or tissue infarction or necrosis

  31. Lesions produced by B. ranarum are characterized by an acute and/or chronic inflammation in association with broad, irregular, erratically septate hyphae, surrounded by a distinctive eosinophilic sheath

  32. Culture of the fungus is the only way to identify correctly the species.

  33. Immunodiffusion test has been used in several patients and claims 100% specificity specificity and may have a prognostic value. Kaufman et al, J Clin Microb 1990;28:9:1887

  34. The first case described of the infection was in a pt from Indonesia by Joe et al in 1956 • Approximately 300 cases (90% cutaneous) have been reported in the World Literature, mostly from Tropical Asia, Africa and South America • A majority of cases have been in children under 10 years of age

  35. In 1994, a healthy 8-year-old boy reported as a case of invasive retroperitoneal infection due to B. ranarum based on histopath who did not respond to high dose Ampho B but the mass resolved completely in 6/52 in response to K1 saturated solution orally Ann Trop Paediatrics 1997;17:161

  36. The 5th case was a 49-year-old lady who presented with GIB mimicking Crohn’s disease with no response to mesalamine and steroids • Diagnosed histopathologically • Responded clinically to oral itraconazole Smilack et al, Gastroenterology 1997;119:250

  37. In 1996 B. ranarum involving the rectum was reported from Kuwait, in a 30-year-old man presented with PR-bleed and polypoid mass • Dx confirmed by culture • Responded to antifungals (Ampho B + ketoconazole) Khan et al CID 1998;26:521

  38. Am J Clin Pathol 1999;112:610

  39. Lyon et al conducted a case-control study to generate hypotheses about potential risk factors in the reported few cases of GIB in AZ, between 1994 to 1999. • According to their results they considered: • Ranitidine • Smoking • Digging earth as of one’s job

  40. The length of residence in AZ to be associated significantly with GIB

  41. Some factors did not reach statistical significance, including: • Steroids • Use of over-the-counter drugs • Animal contact • Eating unwashed vegetables • One of the cases had a Hx of PICA daily for years before the Dx of GIB CID 2001;32:1448

  42. Currently, there is no means of preventing this infection or even identifying those at risk for development of this disease • Early detection of the disease seems to be the best hope of reducing the serious morbidity and mortality associated with long-standing disease

  43. Based on the limited information, it appears that optional treatment of GIB combines surgical and medical methods • Pts should undergo resection and debridement of all affected tissues; followed prolonged antifungal Rx CID 2001;32;1448

  44. Clinical failures have been described in association with Ampho B Mycopathologia 1986;95:101 Am Trop Paed 1997;17:161 CID 1999;28:1244

  45. Ketoconazole has been shown to be effective in both in vitro and in vivo studies AAC 1984;25:413

  46. The best choice of antifungal agent is not clear, but itraconazole seems to have the best results Mycopathologia 1986;95:101 Am J Kidney Dis 1997;29:620 Am J Clin Pathol 1999;112:610 CID 1998;27:663 CID 1999;28:1244 CID 2001;32:1448

  47. In general Basidiobolus spp displays low MICs of itraconazole 0.25 g/ml, ketoconazole 0.5 g/ml • MICs of 0.1 – 1.0 g/ml found to be inhibitory JAC 1999;44:557 Rev Inf Dis 1987;9(Suppl 1):S15

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