Prof. H. Herry Garna, dr., Sp.A(K), Ph.D

1. FEVER AND RASH Prof. H. Herry Garna, dr., Sp.A(K), Ph.D Infection – Tropical Disease Subdivision Department of Child Health, Faculty of Medicine Padjadjaran University, HasanSadikin General Hospital Bandung

2. Introduction • Fever is often the first symptom noted by parents, common problem in clinic • Wide range of severity:  self limiting disease  life-threatening • Wrong first suspicion  fatal outcome • It is more likely to be caused by infection, but any inflammatory, neoplastic, immunologic or traumatic event can generate fever

3. Introduction • Knowledge of differential diagnosis is very important • Diagnosis - Accurate anamnesis -Physical examination - Supporting examination

4. Differential Diagnosis • Past history of infectious disease and immunization • Type of prodromal period • Feature of the rash • Presence of pathognomonic or other diagnostic signs • Laboratory diagnostic tests

5. Differential Diagnosis • Feature of the rash * Category: - Macular or maculo-papular: Morbilli, rubella, roseolainfantum, scarlatina - Papulo-vesicular: Varicella, herpes zoster, variola * Character: discrete or confluent * Distribution, duration * The appearance associated with fever?

6. Etiologic Agents Infectious Diseases • Virus Classic viral exanthema: Measles, Rubella, Varicella Zoster Virus (VZV) Parvovirus, Roseola (HHV 6 and HHV 7) Others: HSV, EBV, HBV, Enterovirus, Dengue • Bacteria Scarlet fever, meningococcemia, typhoid fever Staphylococcal infection (sepsis, toxic shock syndrome)

7. Etiologic Agents • Mycoplasma • Rickettsia Noninfectious Diseases • Allergic: food, drugs, toxin, serum sickness • The etiology remains elusive: Kawasaki disease

8. Anamnesis • Demographic data • Appearance of rash • History of exposure • History of health before • History of disease in the family • Other complaint

9. Anamnesis Demographic Data • Age: neonate, infant, older children • Sex • Ethnic/race : Kawasaki disease ? • Season: winter or dry season or not specific • Certain geographic: endemic

10. Anamnesis Appearance of rash • Location and distribution • Expansion and evolution • Correlation between rash and fever  in the period of high fever (morbilli)  in the period of decreasing fever (roseolainfantum) • Pain or itching (drug eruption: itching)

11. Anamnesis History of Exposure • Contac t with similar disease (house, others) • Travel • Pet, insects • Medicine or other medical measures • Immunization

12. Anamnesis History of health before • History of disease before • Growth and development • History of recurrent disease History of disease in the family Autoimmun ?

13. Anamnesis Other complaint • Local complaint (specific organ) • Systemic complaint (multiorgan/multisystem diseases)

14. Physical Examination • General condition/severity of disease • Characteristic of rash • With enanthema • Other physical disorders

15. Physical Examination General condition/severity of disease • Meningococcemia, Staphylococcal toxic syndrome Characteristic of rash Macule, papule, maculo-papule • Vesicle, pustule, bulla • Petechiae or purpura • Erythroderma: diffuse or local

16. Nonblanching lesions • Petechiae, purpura, and echymosis • Difference size • Petechiae diameter <2 mm • Purpura 2 mm–1 cm • Echymosis diameter >1 cm

17. Physical Examination With enanthema • Mouth: Hand-foot-mouth disease? Buccal mucosa, palatum, pharyng, and tonsil • Genital mucosa Others • Arthritis, eye disorders, cardiac disorders • Hepatomegaly, splenomegaly, lymphadenopathy

18. Diffential Diagnosis of Fever and Rash

19. Morbilli (Measles, Rubeola) Clinical Appearance • Incubation period: 10–12 days • Three stadia: prodromal—eruption— convalescents • Prodromal: 3–5 days 3 C (Coryza, Conjunctivitis, Cough), fever, Koplick’s spots • Eruption: high fever (40–40,5°C)  Typical rash: - Maculo-papularerythromatous - Confluence-general - Start from backside of ear (head)  body and upper arm  lower extremities during 3 days  whole of body

20. Morbilli • Endemic in developing countries • Effective immunization program  cases decreasing  prone to older age group • Lesion particularly at skin, mucous membrane, conjunctiva • Serous exudate, mononuclear cell predominant

21. Diagnosis • Anamnesis * Symptoms * History: contact, immunization • Clinical signs * Typical • Laboratory examination * Leukopenia * Relative lymphocytosis

22. Clinical Manifestations of Morbilli

23. Rash distribution from head to lower extremities Measles Koplick’s spots Conjunctivitis

24. Morbilli Complications • Acute otitis media (10–15%) • Pneumonia interstitialis (50–75% with radiologic abnormalities) • Myocarditis and pericarditis • Encephalitis (1/1,000 cases) 7–10 days after rash appearance (1/3 dead, 1/3 physical defect, 1/3 recover ) • Subacutesclerosingpanencephalitis (SSPE) (0,2–2 /100,000 morbilli, meanincubation 7 years) CFR almost 100% after 6–9 months

25. Complications • Persistent diarrhea • Exaserbation of tuberculosis (TBC) • Keratoconjunctivitis blindness • Secondary bacterial infection of skin • Noma

26. Rubella (German Measles) • Prodromal sign: +/- • Rash: short period  3 days • Typical sign: lymphadenopathypostauricular, suboccipital, posterior colli • Problems in pregnant women  congenital rubella syndrome

27. Clinical Manifestations • Incubation period: 15—21 days • Mild prodromal sign: - mild fever - adolescent: more severe • Rash: maculopapular face  centrifugal to neck  trunk, extremities  24 hours all of body  resolve in 3rd day

28. Congenital Rubella Syndrome • Depend on gestational age  Abortus  Stillbirth  Congenital anomaly • Gravida 1–4 weeks: 61% 5–8 weeks: 26% 9–12 weeks: 8%

29. Congenital Rubella Syndrome • Opthalmologic: Cataract - Micropthalmia Glaucoma - Chorioretinitis • Cardiac: Septal defect - PDA • Neurologic: Meningoencephalitis Microcephaly Mental retardation • Auditoric: Sensorineural deafness

30. Exanthema Subitum (RoseolaInfantum) • Acute infection caused by human herpes virus 6 (some HHV 7) • Mostly in infant • Sporadic (sometimes epidemic) • Typical feature: - Severity of clinical sign unproportionally with degree of fever - Simultaniously resolve of rash and clinical sign

31. Clinical Manifestation • Incubation period: 7–17 days (mean 10 days) • Most common in 6–18 months old • Fever - abruptly high: 39,4–41,2°C - duration: 1–5 days (mostly 3–4 days) - convulsion can occur • Mild clinical sign: mild pharyngitis and coryza • Rash: not specific: macule/maculopapular, rose color  chest  extremities and neck  face • Appear while temperature has return to normal • Disappear on 1–2 days with normal skin

32. Prognosis • Particularly good prognosis • Bad prognosis: Hyperpyrexia with persistent convulsion

33. Scarlet Fever - Scarlatina Clinical manifestation • Incubation period: 1–7 days (mean: 3 days) • Acute symptoms: high fever—headache— vomiting—chills • Signs: severe pharyngitis hyperemia— edema— exudate—dysphagia • Sometimes abdominal pain • Enlargement of lymph node

34. Scarlet Fever- Scarlatina Typical rash • Erythroderma diffuse (red sandpaper) • Reddish macule/papule  blanching on pressure • Firstly on axilla, groin, and neck  24 hours all of body • Petechiae can occur • Rash at chin and forehead (confluence): circumoralpalor • Usually: palms and soles of feet

35. Scarlet Fever- Scarlatina • Tongue: white thick membrane (white strawberry tongue) • After several days : peeled off  papule (red strawberry tongue) • Pintpointpetechiae in the flexures produce a linear purpuric pattern (pathognomonic)(Pastia’s lines)

36. Scarlet Fever (Scarlatina) • A beta-hemolytic Streptococcus group  pyrogenic toxin (erythrogenic toxin) Desquamation occur from end of 1st week to 6th week of disease Diagnosis: History and physical examination Pharyngeal swab: bacterial culture Serologic: ASTO/ASLO/ASO Complete blood count: leukocytosis CRP increased or +: not specific

37. Scarlet Fever- Scarlatina Desquamation of rash after 1 week, especially in hand and foot

38. Complications • Local spread/per continuitatum: - Sinusitis – otitis media – mastoiditis - Retro/parapharyngealabcess - Brochopneumonia - Servical adenitis • Hematogenic spread • - Meningitis – osteomyelitis – arthritis (septic) • Non suppurative (late) complications - Acute rheumatic fever - Acuteglomerulonephritis

39. Dengue Fever (1) • Incubation period: 3–14 days • Fever: suddenly high •  disappear: day-3 or 4  recover or •  dicrease: day-3 atau 4 , and appear again • after 1–3 days  camel saddle •  Long of fever: 5–7 days

40. Dengue Fever (2) • Other complaint • Headache, retro orbital pain • Joint pain, back pain (backborne fever) • Weakness, malaise • Flushing: face, neck • Photophobia, cough

41. Dengue Fever (3) Skin rash  Primary rash Rash: morbilliform (maculopapule): chest and joint fold  Secondary rash After day-4, especially day-6 or day-7 Maculopapule/petechiae /purpura/mixed Confluence: usually hand and foot Sometimes itching

42. Dengue Fever (4) • Hemorrhage ? • Although not usual  hemorrhage • - petechiae (skin) • - epistaxis • - gum bleeding, vomiting/with blood • - menorrhage

43. Pattern of Fever in Dengue Infection 40 oC 39 oC 38 oC 37 oC 36 oC I II III IV V VI VII VIII Primary rash Secondary rash

44. Dengue Virus Infection Petechia Flushing

45. Secondary rash (convalescent rash)

46. Meningococcemia • Etiology: Neisseriameningitidis (meningococcus) • Clinical manifestations • Acute fever, suddenly high • Hemorrhagic manifestations: petechia, purpura (fulminant) • Progressive severe  meningitis, sepsis, septic shock

47. Meningococcemia

48. Varicella/Chickenpox Clinical manifestations • Prodromal:1–2 days, mild fever • Papularerythromatous  vesicle  pustule crusta • Distribution of rash from body to face  neck and extremities • Pruritus +++ • Mucous membrane • Spesific: several kinds of rash in the same time

49. Varicella/Chickenpox Complication • Pneumonia (rare in children, high mortality in immunocompromised hosts • Cerebellar ataxia (1/4.000: age <15 yr) (Develops 7 to 10 days into the disease, excellent prognosis) • Transveremyelitis, Guillain-Barre syndrome • Hemorrhagic: thrombocytopenia

50. Varicella/Chickenpox Complication • Superinfection - local: S. aureusor GABHS: cellulitis - systemic: GABHS: sepsis, necrotizing fasciitis, streptococcal toxicshock syndrome • Reye Syndrome Persistent vomiting, decreased mental status, liver dysfunction Associated with salicylate-containing products Avoid aspirin in varicella !!!