Interhospital Pediatric Chest Conference Queen Sirikit National Institute of Child Health

4/10/2007

Patient profile เด็กหญิง อายุ 3 เดือน ภูมิลําเนา จ.แพร Chief complaint ไข ไอ หอบ 2 วัน Present illness 2 เดือนกอน มีตุมหนองที่ทายทอยขวา ไดยาปฏิชีวนะทาจากคลินิก 1 เดือนกอน มาตรวจที่ร.พ.เด็กดวยปญหาตุมหนองที่ทายทอยขวาไมดขีึ้น ไดรับการรักษาโดยการทํา I&D และยา dicloxacillin 4 วันตอมาเด็กเริ่มไอมีเสมหะ ไขไมสูง น้ํามูกใส ไมหอบเหนื่อย มาร.พ.ได erythromycin,bromhexine,paracetamol อาการดีขึ้น 2 สัปดาหกอน มีไอเปนชุดๆ ไขไมสูง หอบหลังไอ สําลักนมบอย ไมเขยีว 2 วันกอนไข ไอ หายใจหอบเหนื่อย ถายเหลว 2-3 คร้ังตอวัน จึงมาตรวจที่ ร.พ.เด็ก Past history บุตร 2/2 มารดาผลเลือดปกติ คลอดครบกําหนดที่ ร.พ.วชิระ B.W 3,050 gm. ไมเคยหอบมากอน, วัคซนีครบตามนัด Development ปกต ิ Nutrition breast feeding Family history มารดา 19 ป แมบาน สุขภาพแข็งแรง บิดา 26 ป รับจางกอสราง สุขภาพแข็งแรง ตาเปนโรคปอดเมื่อ 1 0 ปกอนไดรับการรักษาที่ ร.พ.รัฐบาล แตยังมอีาการ

ไอบอย ระหวางนี้รับการรักษาที่ ร.พ.รัฐบาล อีกแหงหนึ่ง บอกเปนโรคปอดเรื้อรังไมไดใชยาประจํา ตาสูบบุหร่ีจัด

Physical examination GA A Thai girl, alert, tachypnea and dyspnea, no cyanosis V/S T 38 °C, PR 130/min, RR 60/min BW 4.2 kg (< P3) HEENT AF 2x2 cm, abscess Ø 1.5 cm. at Rt. Occipital area CVS Normal heart sound, no murmur Lung Subcostal retraction, rhonchi and wheezing both lungs Abdomen Soft, mild distension, liver 3 cm. below RCM (span 7 cm.), Spleen not palpable LN Not enlarged

Problem list 1. Fever for 2 wk 2. RTI with Respiratory distress 3. Questionable Tbc contact 4. Hx of chronic skin infection 5. Poor weight gain

Investigation CBC Hct 31.7 %, Hb 10.3 g/dl, WBC 19,600 /mm3.(N 47%, L40%, Mo11%, ATL2%) Plt. 633,000 UA Sp.gr. 1.025, pH 6.0, pro 1+, ket 1+, WBC 3-5, RBC 0-1 ABG ( O2 Box 10 LPM) pH 7.463, Pco2 32.6 mmHg, Po2 90.2 mmHg, HCO3 22.8 mmol/L, BE 0.5 mmol/L LFT TP 4.48 g/dl, Alb 2.72 g/dl, Glo 1.76 g/dl, Alk 91 U/L,Chol 103 mg/dl, TB 0.4/ DB0.18 mg/dl, AST 49/ALT 27 U/L LDH 946 U/L ( 212 - 423 ) Gastric wash for AFB x 3 day negative Tuberculin test 0 mm. PCR for TB negative Anti- HIV negative Ig level normal Ig G subclasses normal T and B cell function normal DHR negative TS for modified AFB negative TS for viral study negative for Influenza A/B,Parainfluenza 1/2/3, Adenovirus, RSV TS for fungus negative TS for PCP negative Melioid titer negative (titer 1:20) Bone marrow biopsy unsatisfactory for evaluation Bone marrow aspiration normal cellularity, normal megakaryocyte M:E:L = 68:23:5, EO 4 %

CXR

CT Chest

Hospital course 17-4 On O2 box 10 LPM, Start Cefuroxime 18-4 On ETT , Ventilator เปลี่ยน ATB :Bactrim (R/O PCP) + Ceftriaxone 19-4 Add Amikin 22-4 Off Ceftriaxone, Amikin Start Meropenem 24-4 Off Bactrim 26-4 Add Vancomycin 27-4 CT Chest Off Meropenem, Vancomycin Start Sulperazone 28-4 CXR: พบ massive Rt pneumothorax, on ICD On HFOV 3-5 Median sternotomy Excision tumor, thymectomy and lung biopsy Operation : Total thymectomy size 5.5 x 3.5 x 1.8 cm. Excision of anterior mediastinal tumor: brownish cystic mass size 5 x 4.6 x 3.1 cm. with gelatinous-like content Lung biopsy of LUL and RLL Pathological report : The immunohistochemical studies show tumor cells reactive for CD1a, S100. The CD20, CD15 and CD3 are non-reactive

Thymus gland: Histiocytosis-X involving the thymus gland.

Mild thymic hyperplasia seen. Final diagnosis is Histiocytosis-X

5-5 Add Amikin 16-5 Off HFOV, on SIMV mode

BMA, BM biopsy Start VCR+Prednisolone

18-5 Off ETT, On O2 Box 10 LPM Off Sulperazon (ไดยา 20 วัน)

Off Amikin (ไดยา 14 วัน) 24-5 Film bone survey : no definite bone lesion 30-5 CT chest (2nd) 2-6 D/C F/U Hemato Clinic ได Chemotherapy: Vinblastine, prednisolone, VP-16, 6-MP F/U Chest Clinic เดก็ยังมีหายใจเรว็บาง ไมหอบ ไมมีไข P.E. lungs:Clear CXR พ.ค.49 CT Chest พ.ค. 49 CXR ต.ค. 49 CT Chest ต.ค. 49

CXR ส.ค. 50 CT Chest ส.ค. 50

Pulmonary Langerhans’ cell histiocytosis (PLCH) Occurs predominantly in adult cigarette smokers PLCH as spectrum of Langerhans’ cell histiocytosis (uncontrolled proliferation and infiltration of

various organs by Langerhans’ cell) Organ systems involved by LCH may include skin, bone, pituitary gland, lymph nodes and lungs LCH ~ 3 times more common in children than adults Pulmonary involvement much more common in adults with LCH, lungs affected in 50% of children

who have multisystem disease Rare cause of ILD in children

Epidemiologic features Occurs principally in young adults ages of 20-40 years, can present in other age groups but rare in

children younger than 15 years Sex distribution of PLCH varies among studies Large surgical lung biopsy series of patients with interstitial lung disease identified PLCH in 5% of

specimens Principal epidemiologic factor associated with cigarette smoking Smoking also may precipitate recurrence of disease in transplanted lungs of patients with PLCH,

conversely, smoking cessation may result in objective improvement of disease Although the epidemiologic association between smoking and PLCH is strong, some patients with

biopsy proven PLCH have no history of active, past or second-hand smoking Other potential role for PLCH are genetic factors and viral pathogens

Pathogenesis

Pathologic finding The lungs contain yellow or grey nodules and subpleural cysts, predominantly in upper lobes, size

from 1mm-1.5cm Nodules contain mainly atypical histiocytes (Langerhans cells) and eosinophils with few lymphocytes Infiltrate mainly peribronchiolar but also present in alveolar wall and around small vessels/capillaries EM allows definitive identification of LCH through demonstration of specific intracytoplasmic

organelles called Birbeck granules LCH typically identified by staining for the S-100 protein and the CD-1a antigen

Birbeck granules

S-100 CD-1a

Clinical features Commonly present with non-specific respiratory symptoms (cough, exertional dyspnea) 25% of patients are asymptomatic at the time of presentation or have a mild “smokers cough” ,

spontaneous pneumothorax is the presenting symptom ~10-15% of patients, constitutional symptoms found upto 1/3 of patients

In children presented with FTT,breathlessness Auscultation of the lungs frequently normal, digital clubbing is unusual In advanced stage of the disease, decrease breath sounds and prolonged expiration Pleural effusion(exudative) very uncommon

Radiologic features Lung volumes may be either normal or increased Hilar lymphadenopathy is unusual Fine or coarse reticular or nodular infiltrates in the upper and midzones with sparing costophrenic

angles If disease progress small cysts or bullae appear and eventually fibrosis and “honeycombing” HRCT : nodules and cysts that predominantly upper lung zones with relative sparing of lung bases

cyst often bizarre shaped, variable in size and typically have a thin wall (≤ 1 mm.) advanced stage, confluent cysts may be form, difficult to distinguish from emphysema PFT, V/Q scan and DLCO

PFT finding depend on when the test is performed during the course of the disease(variable pattern) v./Q. scan : not specific(ventilation more impaired than perfusion) DLCO : reduced is likely to be the consequence of involvement of the pulmonary vascular

compartment and parenchymal disease Bronchoscopy

Bronchoscopy with transbronchoscopic lung biopsy has low diagnostic yield 10-40% (because of the patchy distribution of nodular lesions in PLCH and the small amounts of tissue obtained)

Analysis of BAL fluid also has a small, but appreciable diagnostic yield An increase in BAL CD1a cells > 5% occurs almost exclusively in PLCH

Lung biopsy Surgical lung biopsy (either by thoracotomy or thoracoscopic lung biopsy) remains the “gold

standard” method with the greatest diagnosis yield because of the large portion of tissue obtained

Management Patients with persistent pulmonary or constitutional symptoms or patients who demonstrates

progressive decline in lung function, corticosteroid therapy is often used (Prednisolone 0.5mg/kg) Screening echocardiography for pulmonary HT should be considered in all dyspneic patients Various chemotherapeutic agents, such as 2-chlorodeoxyadenosine, vinblastine, MTX,

cyclophosphamide, etoposide and etanercept have been tried in patients with progressive PLCH or multisystem LCH that is unresponse to corticosteroid therapy

Prognosis and long term outcome Asymptomatics or minimally symptomatic patients have a relatively good prognosis with

stabilization or spontaneous improvement, especially with cessation of cigarette smoking Currently, no good clinical marker to identify patients who are at risk for progressive disease Variable prognosis ranging from excellent (spontaneous remission) to lethal in children Retrospective studies have identified various factors associated with adverse clinical outcome

-extremes of age -multisystem involvement -prolonged constitutional disturbance -extensive cysts and honeycombing on chest radiograph -markedly reduced DLCO -low FEV1/FVC ratio -corticosteroid therapy at time of F/U -high RV/TLC ratio

Serial PFT every 3 months in the first year after diagnosis to identify patients who are likely to develop progressive disease

Adult patients with PLCH seem to have an increased risk of developing malignant neoplasms (lymphoma, MDS, and various epithelial cancers)