This document provides information on fever with rashes, including: 1. It describes the causes and characteristics of fever and rashes. Fever is caused by pyrogens or cytokines during infection or inflammation, while rashes can result from infectious organisms, toxins, autoimmune responses, or vasculature involvement. 2. It outlines the approach to evaluating a patient with fever and rashes, including taking a thorough history, examining the rash characteristics, and performing laboratory tests. Differential diagnoses are made based on signs and symptoms. 3. Common infectious diseases that present with central or peripheral maculopapular rashes are described, such as measles, rubella, and Rocky Mountain spotted fever

1. APPROACH TO FEVER
WITH RASHES

2. FEVER: an elevation of body temperature above the normal
range of 36.5-37.5 degree Celsius (97.7-99.5 F) due to an
increase in the hypothalamic set point.
CAUSE:
1) Pyrogens: microbial products,microbial
toxins(endotoxin),or whole microorganisms.
2) Pyrogenic Cytokines produced during infection and
inflammatory process- IL-1,IL_6,tumor necrosis factor
(TNF),ciliary neurotropic factor(CNTF), and interferon(IFN).

3. RASH is a change of the skin which affects its
color,appearance, or texture. It may occur due to:
1) Multiplication of infective organism in the skin (e.g, HSV)
2) Toxin produced by organisms acting on skin structures
3) Autoimmune destruction of skin due to inflammatory
response against infecting microbes
4) Involvement of vasculature--
vasoocclusion,necrosis,vasodilatation.

4. FEVER WITH RASHES
A skin rash is a symptom that appears during the course of a
systemic or localised disease.
Skin rashes that appear during febrile illnesses are infact caused
by various infectious and non infectious cause.
For clinical diagnosis of disease accompanied by skin rash and
fever,a complete history must be taken ,including recent
travel,contact with animals,medications.
Rashes time of onset and its
characterstics(morphology,location,distribution) could be helpful
in the diagnosis .

5. PRIMARY SKIN LESIONS
1. MACULE – Circumscribed area of change in normal color,with no skin
elevation,may be any size.
2. PAPULE- Solid,raised lesions upto 0.5cms in greatest diameter
3. NODULE-Similar to papule but located deeper in dermis or subcutaneous
tissue.
4. PLAQUE- Elevation of skin occupying a relatively large area than in
relation to height.
5. PUSTULE-Circumscribed elevation of skin containing purulent fluid of
variant character.
6. VESICLE- Circumscribed ,elevated,fluid containing lesions less than 0.5cms
in diameter
7. BULLA- Same as vesicle but lesion is more than 0.5cms in diameter.

6. 8.NON PALPABLE PURPURA-Flat lesions that is due to bleeding into the
skin, if<3mm in diameter,the purpuric lesions termed as PETEICHAE,
If >3mm in diameter they are termed as ECCHYMOSIS.
9.PALPABLE PURPURA- Is a raised lesions that is due to inflammation of
the vessel wall(vasculitis) with subsequent hemorrhage.
10.ULCER- Is a defect in the skin extending atleast into the upper layer
of the dermis.

9. HISTORY
EXPOSURE HISTORY
1. Drug ingestion within the past 60 days
2. Travel outside the local area
3. Occupatrional exposure
4. Sun exposure
5. Immunizations
6.sexually transmitted disease exposure,including risk factors for
infection with human immunodeficiency virus(HIV)
7. Exposure to febrile or ill persons within the recent past

10. 8.Exposure to wild or rural habitats,insects,arthropods and wild
animals
9. Exposure to outdoor water sources such as lakes,streams or oceans
10.Pets,animal exposures and habits.
11. Factors affecting immunologic status-chemotherapy,corticosteroid
use,use of immune modulators,hematologic malignancy,solid organ or
stem cell transplantation and functional or anatomic asplenia
12. Valvular heart disease including heart valve replacement
13. Prior illnesses, including a history of drug or antibiotic allergies.

11. DETAILS ABOUT THE RASH:
1.Site of onset
2.Rate & direction of spread
3.Presence or absence of pruritis
4.Temporal relationship of rash and fever

12. PHYSICAL EXAMINATION
1.Vital signs
2.General appearance
3.Signs of toxicity
4.Presence and location of adenopathy
5.Presence and morphology of genital,mucosal or conjunctival lesions.
6.Detection of hepatosplenomegaly
7.Presence of arthritis
8.Signs of nuchal rigidity,meningismus,or neurologic dysfunction
9.Presence of primary lesion or secondary lesion and its pattern.

13. EXAMINATION OF RASH
Characterize the lesions,both individually and collectively,according to:
1.morphology and arrangement
(annular,linear,serpiginous,dermatomal,etc)
2.distribution (isolated versus generalized,bilateral vs unilateral,symmetric
etc)
3.evolution (centrifugal versus centripetal)

14. LABORATORY EVALUATION:
1.non specific tests-CBC,Urine analysis
2.Blood cultures (obtained prior to antibiotic therapy)
3.Serologic tests (eg. dengue,HIV,Hepatitis B etc)
4. Antigen tests (eg.,serum cryptococcal antigen)
5.Fluid from vesicular,pustular,petechial,ulcerative, and bullous lesions
Vesicular lesions- should be unroofed so that base of the lesion can
be swabbed
Herpes simplex and Varicella zoster virus -diagnosed with direct
fluorescent antibody or PCR assays performed on vesicular fluid
Aspirated fluid from pustules and bullous lesions should be Gram
stained and cultured by microbiology laboratory.

15. DIFFERENTIAL DIAGNOSIS OF FEVER AND RASH BASED ON
SIGNS:
1)ARTHRITIS OR ARTHRALGIA:
• Acute meningococcemia
• Allergic purpura
• Disseminated gonococcal infection
• Erythema marginatum
• SLE
• Lyme disease

16. 2)DESQUAMATION:
• Drug hypersensitivity
• Measles
• Rocky mountain spotted fever
• Scarlet fever
• Stevens johnsons syndrome
• Toxic shock syndrome

17. 3)LYMPHADENOPATHY:
Cervical
• Kawasaki
• Rubella
• Scarlet fever
Generalized
• Infectious mononucleosis
• Secondary syphilis
• SLE
Local
• Tularemia

18. 4)MENINGITIS:
• Acute meningococcemia
• Enterovirus (coxackie,echo viruses)
• Lyme disease
• Rocky mountain spotted fever
• Secondary syphilis

19. 5)MUCOSAL MEMBRANE LESIONS:
• Herpes simplex
• Infectious mononucleosis(palatal petechiae)
• Measles (koplick’s spots)
• Scarlet fever
• Varicella zoster
6)ULCERATIVE /VESICULAR STOMATITIS:
• Hand-foot-mouth disease
• Herpes simplex
• Secondary syphilis
• SLE

20. 7)PALM SOLE INVOLVEMENT
• Acute meningococcemia
• Atypical measles
• Dengue
• Drug rash
• Hand-foot-mouth disease
8)RASH PREDOMINANTLY ON EXTREMITIES
• Disseminated gonococcal infection
• Erythema nodosum
• Brucellosis

21. 9)PULMONARY INFILTRATE:
• Atypical measles
• Fat embolism
• Mycoplasma pneumoniae
• Histoplasmosis
• Sarcoidosis
• Varicella zooster

22. CLASSIFICATION BASED ON ERUPTIONS.
1. CENTRALLY DISTRIBUTED MACULOPAPULAR ERUPTIONS
2. PERIPHERAL ERUPTIONS
3. CONFLUENT DESQUAMATIVE ERYTHEMAS
4. VESICULOBULLOUS OR PUSTULAR ERUPTIONS
5. NODULAR ERUPTIONS
6. PURPURIC ERUPTIONS
7. ERUPTIONS WITH ULCERS AND/OR ESCHARS

23. 1.CENTRALLY DISTRIBUTED MACULOPAPULAR
ERUPTIONS
Centrally distributed rashes,in which lesions
are primary truncal,these are the most common
type of eruption.
A. ACUTE MENINGOCOCCEMIA
Caused by Neisseria meningitidis,it is
classically presents as a peticheal eruption,but
initial lesions may appear as blanchable macules
or papules.
Purpura of extremities – if present
suggestive of DIC-Purpura fulminans

24. B. RUBEOLA(MEASLES-1ST DISEASE)
Caused by Paramyxoviruses
Lesions are discrete that spreads from hairline downward usually
sparing palms and soles.
Koplik spots- 1-2mm whitish or bluish lesions with an erythematous
halo on the buccal mucosa,these are pathognomonic for measles and
generally seen during the first 2 days of symptoms.

25. C. RUBELLA- THIRD DISEASE
Caused by Togavirus
Rashes spreads from hairline downward ,claring as it spreads.
Forchheimer spots- palatal peteichae.
Post aural and suboccipital adenopathy and arthritis are common
among adults.

26. D. ERYTHEMA INFECTIOUSM- FIFTH DISEASE
Caused by Parvovirus B19
Rashes develop after fever has resolved as a bright blanchable
erythema on the cheeks(slapped cheek) with perioral pallor.
Adults with fifth disease often have arthritis and fetal hydrops in
pregnant women.

27. E. INFECTIOUS MONONUCLEOSIS
Caused by Epstien Barr virus.
Diffuse maculopapular eruptions,urticaria,palatal petetichae with
periorbital edema.
Patient may also have hepatosplenomegaly,pharyngitis,cervical
lymphadenopathy,atypical lymphocytosis.

28. F. EPIDEMIC TYPHUS
Caused by Ricketsia prowazekii,Exposure to body lice.
Maculopapular eruption appearing in axillae,spreading to trunk and
later to extremities(usually spares face,palm,soles), evolves from
blanchable macules to eruption with peteichae.

29. G. ENDEMIC TYPHUS
Caused by Ricketsia typhi
Rashes are usually Maculopapular eruption,usually sparing palms
and soles, usually caused by the exposure to the rodents

30. H. SCRUB TYPHUS
Caused by Orientia tsutsugamushi
Rashes are diffuse macular rash starting on trunk,eschar at the site
of mite bite.
Patient may also have flu like symptoms with regional
lymphadenopathy,mortality upto 30% if untreated.

31. i. LEPTOSPIROSIS
Caused by Leptospira interrogans
Rashes are maculopapular with concuctivitis and scleral
hemorrhage. Exposure to water contaminated with animal urine.
Patient will have myalgias,aseptic meningitis,
Fulminant form-Icterohemorrhagic fever(weils disease)

32. J. LYME DISEASE
Caused by the Borrelia burgodferi-bite of ixodes tick vector
Rahes are papule expanding to erythematous annular lesion with central
clearing.
Patient presents with headache,myalgias,fever,photophobia,myocardial
disease,arthritis.

33. K. SYSTEMIC LUPUS ERYTHEMATOSIS
Rashes of SLE are macular and papular
erythema,often in sun exposed areas
,discoid lupus lesions(local
atrophy,scale,pigmentary
changes),periungual telengiectasias,malar
rash,vasculitis causing urticaria,palpable
purpura.

34. L. STILLS DISEASE
Rahes are transient 2-5mm erythematous papules appearing at
the peak of fever on trunk, proximal extremities.
Patient presented with high spiking
fever,polyarthritis,splenomegaly.

35. 2. PERIPHERAL ERUPTIONS
These rashes are most prominent peripherally,begin in
peripheral(acral) areas before spreading centripetally.
1.Rocky mountain spotted fever
2.Secondary syphilis
3.Chickungunya fever
4.Hand foot and mouth disease
5.Bacterial endocarditis

36. A. ROCKY MOUNTAIN SPOTTED FEVER
Caused by Rickettsia ricketsii
Rash beginning on wrists and ankles and spreading centripetally
:appears on palms and soles later in the disease.
Patient presents with headache,myalgia,,abdominal pain,mortality
rates upto 40% if untreated.

37. B. SECONDARY SYPHILIS
Caused by Treponema pallidum
Lesions are copper colored,scaly popular eruption,diffuse but
prominent on soles and palms,rash never vesicular in adults.

38. C. CHIKUNGUNYA FEVER
Rashes are typically occurs in the trunk but also in extremities and
face.
Patient presents with the severe polyarticular,migratory
arthralgias,especially involving the small joints.

39. C. HAND FOOT AND MOUTH DISEASE
Caused by Coxsackie A16 and Enterovirus71 most common causes.
Rashes are tender vesicles,erosions in mouth,papules on hands and
feet with rim of erythema evolving into tender vesicles,shedding of
nails(onychomadesis)can occur after 1-2 months after acute illness.
Coxsackievirus A6 lesions may also be macular,peteicial,purpuric or
erosive, atypical form often extends to perioral area,atypical form
often extends to perioral area,extremities,trunk,buttocks and genitals.
Enterovirus 71 can be associated with brain stem
encephalitis,flaccid paralysis resembling polio or aseptic meningitis.

40. HAND FOOT AND MOUTH DISEASE

41. D. BACTERIAL ENDOCARDITIS
Subacute course(viridans streptococci)- Oslers nodes-tender pink
nodules on finger or toe pads, peteichae on skin and mucosa , splinter
hemorrhage .
Acute course(staphylococcus aureus): Janeway lesions(painless
erythematous or hemorrhagic macules,usually on palms and soles.

42. BACTERIAL ENDOCARDITIS

43. 3. CONFLUENT DESQUAMATIVE ERYTHEMAS
These eruptions are consist of diffuse erythema frequently followed
by desquamation.
A. Scarlet fever
B. Kawasaki disease
C. Stahylococcal toxic shock syndrome
D. Staphylococcal scalded skin syndrome
E. Stevens Johnson syndrome and TEN

44. A. SCARLET FEVER
Caused by Group A Streptococcus(exotoxins-A,B,C)
Diffuse blanchable erythema beginning on face and spreading to
trunk and extremities, circumoral pallor, sandpaper texture to skin.
Accentuation of linear erythema in skin folds(pastia lines), strawberry
tongue , desquamation in second week.

45. B. KAWASAKI DISEASE
Rash similar to scarlet fever,fissuring of lips,strawberry
tongue,conjunctivitis,edema of hands and feets,desquamation in the
later stages
Cervical adenopathy and coronary artery vasculitis are common.

46. C. STAPHYLOCOCCAL TOXIC SHOCK SYNDROME
Caused by S.aureus(TSST 1,Enterotoxins)
Diffuse erythema involving palms,conjunctivitis,desquamation 7-10
days in illness.
Patient may go for septic shock,MODS and even mortality in 30% of
untreated patients.

47. D. STAPHYLOCOCCAL SCALDED SKIN SYNDROME
Caused by S.aureus phage group 2
Rashes are diffuse tender erythema,often with bullae and
desquamation , Nikolsky sign positive

48. E. STEVENS JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS
Drugs – Antibiotics,anticonvulsant,allopurinol
infection
Erythematous and purpuric macules,sometimes targetoid,diffuse
erythema progressing to bullae,with sloughing and necrosis of entire
epidermis,Nikolsky sign positive,involving mucosal surfaces .
TEN(>30% of epidermal necrosis) is maximal form
SJS involves <10% of epidermis
SJS/TEN overlap involves 10-30% of epidermis.

50. 4. VESICULOBULLOUS OR PUSTULAR ERUPTIONS
A. VARICELLA
B. VARIOLA
C. HERPES SIMPLEX VIRUS INFECTION

51. A. VARICELLA-CHICKEN POX
Caused by Varicella zoster virus
Rashes are macules(2-3mm)evolving into papules,then
vesicles(sometimes umbilicated),on an erythematous base (dewdrop
on a rose petal),pustules then forming and crusting:lesions appearing
in crops,may involve scalp,mouth which are intensely pruritic.

52. B. VARIOLA
Rashes are red macules on tongue and palate evolving to papule
and vesicles. Skin macules evolving into papules,then vesicles then
pustules over week,with subsequent lesion crusting.
Lesions initially appearing on face and spreading centrifugally from
trunk to extremities.
Skin lesions are in any given area are at same stage of development
and there is prominent distribution of lesions on face and extremities
(including palm and soles)

53. C. HERPES SIMPLEX VIRAL INFECTION
Caused by HSV-1(children & young adults) and HSV-2 (sexully active
young adults)
Clinical conditions:
● Herpetic Labialis : small blisters or cold sores on or around the
mouth,fever,sores heal within 2-3 weeks but remains dormant in
fascial nerves,severe pharyngitis with dysphagia,lymphadenopathy
● Herpetic Gingivostomatitis : similar to herpetic labialis but with
greater severity.
● Herpetic Genitalis: clusters of genital sores consisting of inflamed
papules and vesicles on the outer surface of the genitals.

54. Herpetic Labialis Herpetic Gingivostomatitis

55. 5. NODULAR ERUPTIONS
A. Erythema nodosum
B. SWEET’S syndrome

56. A. ERYTHEMA NODOSUM
• Inflammation of fat cells under the skin
(streptococcal, fungal, myobacterial,
yersinial)
• Drugs (sulfas,penicillin,OCP)
• Sarcoidosis
Fever ,weakness and arthralgia with tender
red nodules on extensor surfaces.
Rashes are
large,violaceous,nonulcerative,tender,subcut
aneous nodules.

57. B.SWEET SYNDROME (ACUTE FEBRILE NEUTROPHILIC DERMATOSIS)
CAUSE:
• Idiopathic (classic)
• Malignancy(hematological)
• Yersinial infection
• Drug induced
• Pregnancy
• Inflammatory bowel disease
Rashes are acute, tender, erythematous plaques, nodes,
pseudovesicles, and occasionally blisters with annular or arciform
pattern occur on the head, neck, legs, and arms
Lesions show dense infiltrates by neutrophil granulocytes on
histologic examination.

58. 6. PURPURIC ERUPTIONS
BACTERIAL
• Acute Meningococcemia
• Chronic Meningococcimia
• Disseminated gonococcal infection
• Purpura fulminans
• Thrombotic thrombocytopenic purpura
• Hemolytic uremic syndrome
VIRAL
• Viral hemorrhagic fever
• Coxackie virus A9
• Echovirus
• Epstein-Barr virus
• Cytomegalovirus

59. A. MENINGOCOCCAL INFECTIONS
Caused by: Neisseria meningitidis
PATHOGENESIS: Colonization of URT------penetrate into blood stream--
---go to CNS causing Meningitis,, infect the blood vessel---
Meningococcemia
Rash: Erythematous maculopapular rash initially,petechial or frankly
purpuric over hours,large purpuric lesions in severe cases(purpura
fulminans)

60. B. DISSEMINATED GONOCOCCAL INFECTION
Caused by: Neisseria gonorrhoeae
Rash: peripherally,papules or petechiae evolving rapidly to
hemorrhagic pustules with grey necrotic
center.Papules,bullae,pustules and hemorhagic lesions all may be
present simultaneously.

61. C. PURPURA FULMINANS
An acute,aften fatal,thrombotic disorder due to coagulation in small
blood vessels within the skin.
Rash: Large ecchymoses with sharply irregular shapes evolving into
hemorrhagic bullae and then to black necrotic lesions.

62. D. VIRAL HEMORRHAGIC FEVER
Caused by: Ebola virus and Marburg virus, Dengue, Yellow
fever,Kyasanur forest disease,Lassa virus,Lujo virus
Rash: petechial rash
Clinical features: fever,bleeding diathesis,hypotensive shock( due to
capillary leak)

63. 7. ERUPTIONS WITH ULCERS AND/OR ESCHARS
A.Tularemia
B.Anthrax

64. A. TULAREMIA
Caused by: Franscisella tularensis
Rash: ulceroglandular form:-
erythematous ,tender papule evolves
into necrotic ,tender ulcer with raised
borders.Maculopapular rash may
occur.

65. B. ANTHRAX
Caused by: Bacillus anthracis
Rash: Pruritic papule evolving into painless ulcer surrounded by
vesicles and then developing a central eschar with edema;residual
scar