DR. BALDEV S. PRAJAPATI

Transcription

1 DR. BALDEV S. PRAJAPATI D. Ped; MD (Ped.); Gold Medalist FIAP; MNAMS. FICMCH HOD & Professor, GCS Medical College, Hospital & Research Centre, Ahmedabad. Popular Teacher Examiner: UG, M.D;DNB Across the country, OSCE Expert. FIAP 2005 Executive Board Member, Central IAP 2002, 2003, 2005, 2006, 2011 Chairperson, ID Chapter, IAP, 2009 Member, IAP Committee on Immunization , President, IAP Gujarat State Branch, 2003 Author : Essential Procedures In Pediatrics Publications : 92

2 Clinical & Diagnostic Features of Cystic Fibrosis

3 Outline Case scenario Cystic Fibrosis (CF) CF in India Basis of CF Clinical Features Laboratory Ixs Sharing our experience Take Home Message

4 Case 1 3 years Male Cough paroxysmal followed by occasional vomiting 20 days, High grade fever 3 days H/o Hosp. 6 times in the past. First Hosp. on 3 DOL for 17 days, diagnosed as septicemia with NEC with prolonged jaundice

5 2 nd Hosp. at age of 17 months for cough, fever and freq. of stool, diagnosed as bronchiolitis 3 rd Hosp. at age of 21 months for fever, cough, freq. of stool and convulsions, diagnosed as acute bronchitis with Rt MZ PN with FS 4 th, 5 th & 6 th Hosp. diagnosed as bronchial asthma (S. IgE 700 IU/ml)

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7 On Exam. FTT Febrile, tachycardia, tachypnoea, RD R/S, Bil. Rhonchi & creps Clubbing grade II

8 Immunoglobulins WNL Tests for HIV Nonreactive

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11 Dr. BSP

12 Dr. BSP

13 Case 2 8 years Male Cough with yellow sputum 7 days, high grade fever 2 days Treated by local pediatrician with cefixime, antipyretics & antitussive. Hb 9.6, TLC 18,000, P 78, CXR Bronchitis Referred for further management

14 H/o. Hosp. 5 times, 4 times for pneumonia & once for diarrhoea H/o. death of one male sibling at age of 9 years due to LRTI & diarrhoea No H/o TB contact Vaccinated for age

15 Wt kg (25.5) Head 50 cms HT 110 cms (125) Temp o F, PR 130/min, RR 44/min, BP 110/60 SPO 2 91% in room air Clubbing grade II Left lower zone AE, Bil. Creps No murmur, No HS, CNS NAD Hb 10.1, TLC 29,200, P 90, ESR 102, CRP 286, RBS, LFT, RFT, S.electrolytes WNL

16 Inj. Ceftriaxone IVF Paracetamol

17 After 48 hours, Temp o F, PR 140/min, RR 50/min. Toxic Left side AE, VR Liver 3 cm, spleen NP

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20 VATS by pediatric surgeon 45 ml thick yellow fluid aspirated, septae broken, sent for culture ICD inserted Pleural fluid Exam. Proteins 2.6 G/dL, sugar 10 mg/dl, cells 260,P 80 Gram s stain Gram ve bacilli Organisms isolated pseudomonas aeruginosa

21 Inj. Ceftizidime for 3 weeks Chest physiotherapy

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23 Problems Recurrent pneumonia Diarrhoea FTT H/o. death of one sibling due to LRTI & Diarrhoea Clubbing Empyema with isolation of Pseudomonas

24 Sweat chloride 104 and 90 meq/l Mutation test +ve Cystic Fibrosis

25 Case 3 5 months Male Freq. of stool 8-10/day, semi solid, foul smell, No vomiting, not gaining wt. FTND, Hosp. CSAB, BW kg H/o operation for meconium cyst on third DOL H/o Hosp. 3 times for diarrhoea & not gaining wt.

26 Wt kg Head 37.5 cms length 53 cms vitals stable, FTT, Abd. distended. No HS CBC WNL, Na meq/l, K meq/l, Cl - 78 meq/l, ABG Metabolic alkalosis Sweat chloride 97 meq/l & 102 meq/l Mutation test of child & parents DF 508 Cystic Fibrosis

27 7 months Female Case 4 Referred for recurrent vomiting, diarrhoea & not gaining weight since age of 3 months H/o Hospitalization ADD with severe dehydration Left upper zone pneumonia with FTT with Hypokalemia & nephrocalcinosis (UI) Born to young, non consanguineous parents. FTND / Hosp / CIAB / BW 2.9 kg FTT, Dehydration ++, Lethargic baby. Referred for further management

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34 Cystic Fibrosis Presenting as Pseudobartter Syndrome

35 Cystic Fibrosis Cystic Fibrosis (CF) the most common life-limiting recessive genetic disorder in Caucasians incidence approx. 1 in 2500 children born in UK Is it extremely rare in India as it was thought of? No, under diagnosed or missed Rarely suspected, if suspected, not confirmed due to lack of investigative facility Exact incidence in India is not known

36 Cystic Fibrosis Authors No. of pts Diagnosed by Bhakoo et al (1968) 01 Histopathology Mehta et al (1968) 13 Sweat Test Mehta et al (1969) 06 Sweat Test Devi et al (1969) 04 Sweat Test Gupte et al (1970) 06 Sweat Test Reddy et al (1970) 12 Autopsy Venkatraman et al (1972) 01 Autopsy Jagdish JS (1989) 01 Sweat Test Sarkar AK et al (1992) 01 Sweat Test Maiya PP et al (1980) 03 Sweat Test

37 Cystic Fibrosis Authors No. of pts Diagnosed by Prasad ML et al (1990) 02 Autopsy Deivanayagam CN et al (1990) 05 Autopsy Bowlers (1993) 09 Sweat Test & Mutation Test Spencer et al (1994) 13 Sweat Test Powers et al (1996) 20 Sweat Test Singh et al (2002) 18 Sweat Test Kabra et al (2003) 120 Sweat Test & Mutation Test Ashavaid et al (2005) 39 Sweat Test & Mutation Test

38 Delayed diagnosis in India leads to severe malnutrition. Malnutrition is the bad prognostic indicator for survival Early diagnosis & appropriate management may improve the outcome

39 Genetics of CF CF gene identified in 1989, more than 700 mutations have been recognized Most common mutation is delta F508, 70% of total cases. Indian subcontinent, it has been reported between 19 & 44%

40 Basis of disease... The basic defect in CF mutation in the gene for chloride conductance channel i.e. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Results in an abnormality of camp regulated chloride conductance by epithelial cells on mucosal surface Leads to dehydration of secretions that are too viscid & difficult to clear Facilitate chronic infections (P. aeruginosa & staph.aureus most common) Once chronic infection is established, organisms are not eradicated

41 Clinical Manifestations 0 to 2 years Meconium ileus (10-15%) Obstructive jaundice Hyponatremia Hypoproteinemia Steatorrhoea (85%) Salty Kiss FTT Bleeding diathesis Rectal prolapse Staph. pneumonia Bronchitis / Bronchiolitis

42 Clinical Manifestations 2 to 12 years FTT Malabsorption Nasal polyposis Intussusception Recurrent pneumonia

43 More than 13 years Clinical Manifestations Chronic pulmonary disease (70%) Clubbing Pancreatic insufficiency Gall stones Azoospermia Abnormal GTT/DM Chronic intestinal obstruction

44 Atypical Manifestations Appendicitis in Naonates / Infants Pancreatitis Cholelithiasis Rectal prolapse Inguinal Hernia Pseudobartter syndrome Infertility Delayed puberty Dehydration - heart exhaution Diabetes Mellitus Portal Hypertension

45 Clinical features consistent with diagnosis of CF Chronic sino-pulmonary disease manifested by, Recurrent LRTIs Chronic cough & sputum production Airway obstruction manifested by wheezing & air trapping Persistent colonization with typical CF pathogens like P.aeruginosa, staph.aureus, Non-typable HIB, Burkholdelia cepacia

46 Clinical features consistent with diagnosis of CF GIT & Nutritional abnormalities Meconium ileus, Intestinal obstruction, Rectal prolapse Pancreatic insufficiency, Recurrent pancreatitis Biliary or multilobular cirrhosis FTT Hyponatremia Salt loss syndrome Acute salt depletion Metabolic alkalosis Obstructive azoospermia

47 Laboratory Tests Sweat Chloride Test Indications Recurrent / Persistent LRTI Malabsorption Meconium ileus Family H/o CF

48 Sweat Chloride Test Method Sweat collection is carried out by pilocarpine Iontophoresis. Chloride conc. is estimated by titration, flame photometry or by using an ion specific electrode

49 Sweat Chloride Test Interpretation If sweat Cl - > 40 meq/l abnormal repeat the test to confirm If sweat Cl - < 40 meq/l Normal Repeat if strong clinical suspicion If 2 values of sweat Cl - done atleast one week apart >60 meq/l with sweat wt > 100 mg CF If sweat Cl - between meq/l suspected CF Repeat the test after 4-8 weeks/mutation test / other ancillary tests If sweat wt < 100 mg Repeat the test after 4-8 weeks

50 Sweat Chloride Test Genotypically confirmed CF & normal sweat Cl - test has been reported, but rare. They have mild symptoms & may first present in adult life with obstructive azoospermia For reliable results, experienced person is more important Available facility in India Very limited Centers

51 Laboratory Tests Other Investigations Chest x-ray Chest CT Scan LFT, RFT, RBS, S.Ca ++, PO 4, Alkaline phosphtase, S.Na +, K +, Cl -, ABG Mutation Analysis for CF GER studies USG Abdomen Culture of secretions to identify airway colonization

52 Suspect cystic fibrosis in children presenting with recurrent / persistent pneumonia, malabsorption and failure to thrive Sweat test facility available NO Yes Do serum electrolytes, arterial blood gas analysis, culture of respiratory secretions. Stool for fat globules >60 meq/l Perform sweat chloride values meq/l < 40 meq/l Look for hypokalemia, hyponatremia, metabolic alkalosis Pseudomonas in airway secretions, numerous fat globules in stool microscopy Repeat Sweat CI Treat as CF if repeat is > 60 meq/l Repeat Sweat CI Persistent borderline, Try to get mutation analysis Follow up as suspected CF, treat with enzyme replacement, vitamin Label as CF after positive sweat test / mutation studies CF is unlikely investigate for alternative diagnosis

53 Prenatal Diagnosis With the identification of genetic mutations in a child & parents CV at around weeks or amniotic fluid cell culture at weeks of gestation

54 Our Experience Total No of patients: 33 Male: 21 Female: 12 0 to 2 years: 04 2 to 12 years: 26 > 12 years: 03

55 Our Experience FTT: 31 Steatorrhoea: 27 Meconium ileus: 02 Meconium peritonitis: 01 Obtructive jaundice: 01 Bronchitis / Bronchiolitis: 08 Recurrent pneumonia: 22 Staphylococcal pneumonia: 12 Pseudomonas Pneumonia: 06 Malabsorption: 30 Clubbing: 28

56 Take Home Message CF is not rare in India & in Gujarat. It is under diagnosed or missed because it is rarely suspected & if suspected, not confirmed due to lack of investigative facility. Exact incidence in India is not known. Clinical presentation varies from neonates to younger children & adolescents. Any pt. presenting with chronic or recurrent sino pulmonary disease, chronic diarrhoea, malabsorption syndrome, FTT, pancreatic insufficiency or salt loss syndrome without any obvious reason should be investigated for CF. Any child with H/o meconium ileus or prolonged jaundice in neonatal period, CF should be ruled out

57 Take Home Message Delayed diagnosis leads to severe malnutrition, malnutrition is the bad prognostic indicator for survival Clinical diagnosis of CF should be confirmed by sweat chloride test. For reliable results, proper technique and experienced person are important. It should be interpreted in context to other factors. Parents & child should be submitted for mutation test Early diagnosis, adherence to standard protocol in management & regular follow up are quite gratifying With identification of genetic mutations in a child & parents, prenatal diagnosis should be performed

58 Thank You