Clinical Pathologic Conference

1. R1曾敏華 / 洪志興主治醫師 Clinical Pathologic Conference

2. Chief complaint • A 5 year-old boy was admitted because of fever off and on with chillness, cough with whitish sputum and chest pain for 3 days.

3. Present illness • About 1 week before this episode (10 days before arrival), he suffered from several times of watery diarrhea. • He had chest wall injury while he was playing with his friend. • 3 days before admission, fever off and on with chillness, cough with whitish sputum and chest pain were noted.

4. Present illness • The pattern of chest pain: -No relieve or aggressive factor -No radiating pain. -Did not improved despite of medication. • 1 day before admission, dyspnea after climbing upstairs and palpitation was also noted. • He was brought to ER on the day of admission, and short of breath, pale lips, pale conjuntivae were found and vomiting for 3 times at ER.

5. Present illness • Throughout the whole course of present illness, he had no skin rash, headache, abdominal discomfort and urinary change. • His appetite and activity were good.

6. Past,Personal and Family History • Past history -Allergic rhinitis -Hydronephrosis, left. -Asthmatic bronchitis -Urethritis -Acute gastritis

7. Past,Personal and Family History • Birth history: -GA: 38 weeks via C/S, Birth weight: 3700 gm • Developmental History: normal • No travel history. • Family history: Grandfather: had been working at mine, (礦物局) driver. : No any family member has the same symptoms like him.

8. Physical examination • Vital sign: PR: ↑ 132 /min (65-110), RR: ↑ 36 /min(20-25), BT: 37 ºC • HEENT: Pale conjunctiva/ lip , grade 1/4 of tonsils, : congested throat • Chest wall: A tender mass 2 × 3-cm in size at his fore- chest wall. : Coarse breathing sound

9. Lab. data 0905(admission) B/R: -WBC:14,620 (5,5-15,5 x10 3) -RBC: 4.72 x10 6(3.9-5.3 x10 6 ) , Hct:33.4% -Hgb: 11.3 ( 6mo-6 yr: 10.5 - 14) Nelson 17 ed Table 439-1 -MCV: 70.9 (6 mo-6 yr: 70-74) Nelson 17 ed Table 439-1 -MCH:24 (24-30) -MCHC:33.8(31-37) -PLT: 244 x10 3(150-450 x10 3 ) -Neut. ↑ 77.1% (54-62%); LYM.:25% (25-33%); Mon.:4.9 %(3-7%); Eos.:0.5 %(1-3%)

10. Lab. data 0907(hospitalization) B/R: -WBC:10,380 (5,5-15,5 x10 3) -RBC: 4.65 x10 6(3.9-5.3 x10 6 ), Hct:33.4% -Hgb: 11.0 ( 6mo-6 yr: 10.5 - 14) Nelson 17 ed Table 439-1 -MCV: 69.7 (6 mo-6 yr: 70-74) Nelson 17 ed Table 439-1 -MCH:23.7 (24-30) -MCHC:34(31-37) -PLT: 234 x10 3(150-450 x10 3 ) -Neut. ↑65 % (54-62%); LYM.:25% (25-33%); Mon.:8 %(3-7%); Eos.:2 %(1-3%)

11. Lab. data • Mycoplasma AB: < 40 (-) • CRP: ↑2.93 (0.17-1.07) • BUN / Cr: 10 / 0.4 • CPK: 50 U/L(5-110); CK-MB: 1 U/L: 2 %(1.7-7.9 %) • Glucose: 158 mg/dL • Na/ K/ Cl: 136/↓3.4/ 100 • Total Ca: 9.3

12. Lab. data • Urine routine: - pH: 6.0 -Protein: +/- -RBC: 0-1/ HPF -WBC: ↑5-10/ HPF (Children 0–5/ hpf ) -Spgr: 1.017

13. Hospital course : • After admission, CxR was taken, and draws blood samples. • He was discharged to home after a series of studies and treatment.

15. Problem list Major problems: • Chest pain • Short of breath/ dyspnea • Chest wall mass • Fever, cough • Vomiting • Diarrhea Minor problem • Pale conjuntivae/ lip • Hyperglycemia • Pyuria (U/R) ?

16. Questions? • Correlation between chest injury and chest pain/ chest mass? • Chest mass location ? Rib, costochondritic joint, intercostal muscle or sternum? • Chest wall mass: Mobile or immobile? Warm/ heat? fluctuant ? • Chest pain: sudden onset or progressive? • Needle aspiration (culture)? Mass biopsy ? • Viral culture (throat)? • CxR ? Patchy infiltration? Hilar lymphoadenopathy? • Body weight loss? Night sweating? FHx of TB? Medication Hx? • EKG ? • Sputum culture?

17. Infectious costochondritis Virus infectious osteomyelitis Empyema necssitatis

20. Chest pain: possible differential diagnosis • Infectious costochondritis: Tietze syndrome • Pleurodynia • Pneumonia: Pyogenic Empyema Necessitatis • Musculoskeletal chest wall pain: Osteomyelitis

21. Dyspnea: possible differential diagnosis Pediatric Respiratory medicine

22. Dyspnea: possible mechanism Pediatric Respiratory Medicine P370 • ↓Pulmonary compliance: Inflammation • ↑Airway Resistance: Airway inflammation & hyperreactivity • ↑Sensory Stimuli: Chest wall • ↑Chemical Stimuli: Hypoxemia, CO2, Acidosis

23. Chest wall lession in childhood: possible differential diagnosis Pediatric respiratory review 2002;3:328-38

24. Chest wall lesions in childhood • A wide range of pathologies. I. Benign lesions: include a. Lipoma /Lipoblastoma: usually painless, occur in the first 2 years b. Neurofibroma: Painless, associated with neurofibrosis type I c. Lymphangioma: Painless,associated with a variety of other syndromes such as asplenia,Noonan’s syndrome, and tuberculosis.

25. Chest wall lesions in childhood d. Haemangioma and AVM : congenital lesions. e. Mesenchymal hamartoma : benign lesion of infancy with most lesions presenting before 2 years of age.

26. Chest wall lesions in childhood II. Malignant lesions: include a. Neuroblastoma: occur before 5 years of age, abdominal mass b. Rhabdomyosarcoma:common found in head/ neck or extremities c. Ewing’s sarcoma, Askin tumour, Primitive neuroectodermal tumours: : all belong to the group of small round blue cell tumor of childhood. : Usually presenting in the second decade of life.

27. Chest wall lesions in childhood II. Manifestations of systemic diseases: e. Leukaemia/ Lymphoma : always be excluded in a child : presenting with multiple bone lesions or bone pain, hematologic finding. f. Langerhans cell histocytosis

28. Chest wall lesions in childhood III. Infections a. Tuberculosis: -TB on the chest wall can occur as an isolated primary infection with no evidence of pulmonary disease - Spread to the chest wall from pulmonary infection may also occur althrough symptoms may be minor - Presentation may be similar to pyogenic abscess or simply an enlarging mass.

29. Chest wall lesions in childhood b. Actinomycosis : rare, may mimic TB with pulmonary infiltration and spread to the chest wall c. Aspergilosis: in immunocompromised patients, usually by local invasion from the lung. d. Progenic abscess : Staphylococcus, Klebsiella infection e. Other infection illness: Strongyloidiasis (Strongyloides stercoralis)糞小桿線蟲

30. Chest wall lesions in childhood IV. Other lesions: a. Pseudo-lesions: found in cildren of early teenage years presenting with a hard lump in costochondral cartilage. : Usually no specific symptoms. b. Thoracic cage anomalies,osteochondroma, hemangiopericytoma

31. Chest wall mass: possibile DDx • Tuberculosis • Actinomycosis • Pyogenic abscess • Strongyloidiasis (Strongyloides stercoralis)

32. Differential diagnosis Chest pain • Infectious costochondritis: Tietz syndrome • Pleurodynia • Pneumonia- Pyogenic Empyema Necessitatis • Osteomyelitis Chest mass • Tuberculosis • Actinomycosis • Pyogenic abscess • Strongyloidiasis • Dyspnea • ↑Airway Resistance: Airway inflammation & hyperreactivity • ↓Pulmonary compliance: Inflammation • ↑Sensory Stimuli: Chest wall • ↑Chemical Stimuli: Hypoxemia, CO2, Acidosis

33. Virus Bacteria Differential diagnosis 1. Pleurodynia 3. Tuberculosis 4. Actinomycosis 5. Pneumonia: Pyogenic Empyema Necessitatis 6. Pyogenic abscess 2. Infectious costochondritis: Tietze syndrome 7. Post viral Osteomyelitis 8.Strongyloidiasis (Strongyloides stercoralis) Parasite

35. 1. Tietze syndrome: infectious costochondritis • Inflammation of the costal cartilages (Costochondritis) with a large, tender, fusiform (spindle-shaped), nonsuppurative swelling at the costochondral or chondrosternal junction. Principles and Practice of Pediatric Infectious Diseases, 2nd ed • Etiology: -Exact cause unclear -Most often idiopathic -Associated with excessive exercise, chest injury or a preceding viral respiratory illness (postinfectious)

36. 1. Tietze syndrome • Epidemiology -Generally occurs in late teens to early twenties, but has been described in young children. • S/s: sharp pain in anterior chest wall, may radiate to back or upper abdomen. : varies in intensity and quality. • PE: Tender by palpation at local site or movements of the arm or shoulder. :May show evidence of tachypnea, tachycardia or systolic HTN. : Distortion of local soft tissue.

37. 1. Tietze syndrome • Diagnostic workup -Made with historical and physical clues. -Biopsy: increased cartilage and lack of inflammatory fibrosis. • Management: NSAIDs, Injections into the painful area with triamcinolone are sometimes curative. Question: Fever ? preceding viral respiratory illness?

38. 2. Pleurodynia Nelson 17ed p1045, Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Etiologic agents are most frequently coxsackieviruses B3 and B5, as well as coxsackieviruses B1 and B2 and echoviruses 1 and 6. Nelson 17ed p1045 • Sex:Males are affected more than females. Half of these patients are younger than 5 years, and 30% are younger than 1 year. • Coxsackievirus B usually causes an asymptomatic or brief upper respiratory tract or gastroenteric infection. Nelson 17ed p1045 • The virus has an incubation time of 1 week in the GI tract and subsequently involves the target organs through hematogenous dissemination.

39. 2. Pleurodynia Nelson 17ed p1045, Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Prodromal symptoms such as malaise, myalgias, headache and diarrhea are followed by sudden onset of fever and pain. Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Involvement of the intercostal and other muscles of respiration results in enhanced pain with deep breathing and a sensation of “pleuritic” pain that can result in splinting of the chest and rapid, shallow breathing. Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Pain, typically located in the chest or upper abdomen, and is spasmodic and can be excruciatingly severe. Nelson 17ed p1045 • During spasms, respirations are usually rapid, shallow, and grunting, pale, sweaty, and shock-like appearance.Nelson 17ed p1045

40. 2. Pleurodynia Nelson 17ed p1045, Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Causes necrosis of the striated intercostal muscles in patients with pleurodynia. • Muscle tenderness can be detected by direct palpation; less commonly, localized swelling is observed ( Sylvest, 1934 ) • Associated symptoms related to the viral infection may include the following: -Upper respiratory tract symptoms, including sore throat, rhinitis, and cough. -Constitutional symptoms, including headaches (50%), fever, and malaise

41. 2. Pleurodynia Nelson 17ed p1045, Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 -GI symptoms, including nausea, vomiting, diarrhea (50%), and in children, abdominal pain (usually in the epigastric area) • Diagnosis: -Viral cultures(throat) isolation of coxsackievirus B in cell cultures . -RT-PCR(throat) -Histologic Findings: Necrosis of the striated intercostal muscles is visible . -Serum creatine kinase is usually elevated because of muscle necrosis. -CxR: reveals clear lung fields; less than 10% of patients have a pleural friction rub or pleural fluid evident on chest radiographs.

42. 2. Pleurodynia Nelson 17ed p1045, Principles and Practice of Pediatric Infectious Diseases, 2nd ed P1183 • Illness usually lasts 3–6 days, but can last up to a couple of weeks. • Illness may occasionally be associated with meningitis, orchitis, myocarditis, or pericarditis. • Management: -Analgesics and limitation of physical activity are helpful in reducing pain, which is generally most severe on presentation and then progressively diminishes during the course of illness (which is typically 4 to 6 days but which may last as long as 3 weeks) ( Warin et al., 1953) • Question: Serum creatine kinase within normal range

43. 3. TuberculosisPrinciples and Practice of Pediatric Infectious Diseases, 2nd ed I. Bony tuberculosis • Osteomyelitis is otherwise most frequently found in the metaphysis of long bones, although theribs, pelvis and skull may be infected. • In children in countries in which TB is prevalent, osteomyelitis is a significant cause of crippling deformity. • Trauma does not predispose to tuberculous osteomyelitis

44. 3. Tuberculosis Principles and Practice of Pediatric Infectious Diseases, 2nd ed • Bony TB may be accompanied by sinus tracts or soft tissue masses. • Diagnosis: -May be difficult because lesions can appear osteolytic or sclerotic on radiography. -Biopsy : acid-fast bacilli (AFB) stains, culture or PCR

45. 3. Tuberculosis Principles and Practice of Pediatric Infectious Diseases, 2nd ed II. Tuberculous abscesses: • May form in most soft tissues, including muscle . • This is usually secondary to contiguous spread of infection but may follow hematogenous dissemination. • The classic abscess site is in the psoas muscle, and such an abscess can occur with or without localizing signs • Cough, diarrhea and vomiting can be happened, but rare and chronic when the pulmonary and gastointestinal were involved. • Question: Contact history? insidious enlarging mass? Chronic steroid usage? Body weight loss? Night weating?

46. 4. Actinomycosis Nelson Textbook of Pediatrics, 17th • Actinomyces israelii , a slow-growing, gram-positive bacteria that are part of the normal oral flora in humans. • Infection caused by these bacteria is termed actinomycosis, which is a chronic, granulomatous, suppurative disease characterized by peripheral spread with extension to contiguous tissue in the formation of numerous draining sinus tracts. • 7% of the patients <10 yr of age. The youngest patient in this series was 28 days old.

47. 4. Actinomycosis Nelson Textbook of Pediatrics, 17th • Actinomycosisis usually not an opportunistic infection, disease has been described in patients receiving corticosteroids and those with leukemia, renal failure, congenital immunodeficiency diseases, and HIV infection • three important sites of Actinomyces infection in order of frequency are cervicofacial, abdominal, and thoracic • Pulmonary actinomycosis may present as fever, productive cough, chest pain, and weight loss. • Infection frequently dissects along tissue planes and may extend through the chest wall or diaphragm, producing numerous sinuses.

48. 4. Actinomycosis Nelson Textbook of Pediatrics, 17th • Diagnosis : confirmed by examining purulent sinus tract drainage for sulfur granules, and by appropriate cultures. • The differential diagnosis of pulmonary actinomycosis includes lung abscess and tuberculosis. • Tx: mainstay of treatment for actinomycosis is prolonged antibiotic therapy (Penicillin) and an appropriate surgical approach to sinus tracts and abscesses.

49. 4. Actinomycosis Nelson Textbook of Pediatrics, 17th Question: Chronic process, underlying immunocompromise status; diarrhea? Vomiting?

50. 5. Pneumonia- Pyogenic Empyema Necessitatis • Pyogenic Empyema Necessitatis: A rare complication of empyema; is a collection of inflammatory tissue that usually extends directly from the pleural cavity into the thoracic wall forming a mass in the extrapleural soft tissues. • The hallmark of empyema necessitatis is a mass • The most common etiologies are tuberculosis and actinomycosis.