Clinical Pathology Conference

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Clinical Pathology Conference

• Stanford Massie M.D.
• October 17, 2006

A 35 y.o. female with a painful, pruritic rash
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If you dont know where you are going, you have
to be careful as you may not get there.
Yogi Berra
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Goals of the talk

• Share my step by step approach to this case
• Review a strategy for dermatologic diagnosis
• Review skin disorders in HIV
• Discuss the differential diagnosis for the key
  findings
• Share some pearls along the way

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Road Map

• Review of the protocol
• Development of a problem list
• Approach to Dermatologic Diagnosis
• Discussion of key clinical findings
• Review and discussion of the final differential
• Selection of the final diagnosis

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The case--HPI

• 35 y.o. female with HIV/AIDS and no prior HAART
  presents to ED with a 2 week h/o
• Diffuse painful and pruritic rash
• Fevers to 103 F
• Myalgias
• Non productive cough
• Features of the rash include
• Started on extremities
• Now involves whole body

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The case--HPI

• She denies TB contacts or recent travel
• No other history of present illness provided
  except for arthralgias noted on the ROS

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The Case Past History

• HIV since 1996, CD4 11 one year ago
• Pneumococcal Pneumonia and Bacteremia 2003, 2005
• Chicken pox as a child
• LE DVT 2005
• Psychiatric issues

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The Case-- Medications

• None reported

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The Case Social History

• Unemployed, unmarried
• Monogamous with boyfriend, but multiple sex
  partners in past
• Uses cocaine daily, denies IDU
• Uses Tobacco and ETOH

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The Case Physical Exam

• VS BP 110/70, Pulse 75, R-18, 100 sat (RA)
  Temp 1018
• Gen thin WF in NAD
• HEENT 3-4 mm ulcers on hard palate
• Neck supple, no LAN
• Pulm CTAB
• Cardiac RRR, no M/R/G
• Abd soft, nontender. No HSM.
• Extr Not reported
• Neuro non-focal

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The Case Skin Findings

• Diffuse polymorphic rash involving face, trunk
  and extremities
• Rash characterized by
• Discrete erythematous papules
• Some with crusted necrotic centers
• Other lesions appearing as pustules

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The Case Laboratory Data

• CBC normal except for microcytic anemia (Hct 27)
• LFTs normal
• Chem 7 normal except for Na 129 (normal AG)
• UA notable for cloudiness, trace prot and blood,
  25-50 WBC and WBC casts

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• If the fresh facts which come to our knowledge
  all fit themselves into the scheme, then our
  hypothesis may gradually become a solution
  
• Sherlock Holmes

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Initial Problem List

• Host Issues
• Exposures
• Features of Present Illness
• Objective Findings

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Initial Problem List

• Host Issues
• HIV/AIDS, low CD4 count, no Rx
• Pneumococcal Bacteremia X2
• VZV as a child
• DVT
• Exposures
• Multiple sex partners
• Daily cocaine use
• (No medications or travel)

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Initial Problem List

• Features of present illness
• 2 week illness with rash, fever, arthralgias, NP
  cough and oral ulcers (hard palate)
• Rash started on extremities and spread to rest of
  body
• Rash painful and pruritic

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Initial Problem List

• Objective Findings
• Ulcers on hard palate (3-4 mm)
• Fever
• Polymorphic rash involving multiple body surfaces
  with signs of pustule formation, central necrosis
  and ulceration
• Hyponatremia
• Microcytic anemia
• Normal LFTs, WBC
• Pyuria with WBC casts

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Revised Problem List

• HIV/AIDS, low CD4 count, no Rx
• Fever
• Diffuse polymorphic rash with erythematous
  papules, pustules and necrosis
• Oral Ulcers
• Pyuria and WBC casts
• Daily Cocaine Use
• Multiple sex partners
• Arthralgias
• Hyponatremia Microcytic anemia

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Key assumption

• To explain all of these findings, we must invoke
  an illness involving multiple systems
• The alternative would be several distinct
  concurrent illnesses
• I will go with Occams razor

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Revised Problem List

• HIV/AIDS, low CD4 count, no Rx
• Fever
• Diffuse polymorphic rash with erythematous
  papules, pustules and necrosis
• Oral Ulcers
• Pyuria and WBC casts
• Daily Cocaine Use
• Multiple sex partners
• Arthralgias

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Approach to Dermatologic Diagnosis Background

• Hundreds of cutaneous diseases
• Variation in appearance
• Dynamic morphology
• The ability to interpret what is observed is
  paramount
• Avoid rapid/hasty judgements

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Approach to Dermatologic Diagnosis PE

• Type of lesion
• Shape of individual lesions
• Arrangement of multiple lesions (scattered,
  grouped etc)
• Distribution of lesions
• Color
• Consistency and feel
• Primary and secondary lesions

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Approach to Dermatologic Diagnosis Background

• An uncommon presentation of a common disease
  occurs more frequently than a common presentation
  of an uncommon disease

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Skin Disease in HIV

• More than 90 develop rash
• Increased risk for rare and common infectious and
  inflammatory skin conditions
• Causes correlate with stage of HIV and CD4 count
• Skin problems tend to be more severe, atypical
  and resistant to treatment
• Drug reactions are common

Zancanaro P et al. J Am Acad Dermatol
200654581-8.
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Skin Disease in HIV

• Once the CD4 count skin conditions often chronic
• The skin of pts with advanced HIV is
  hyper-reactive
• HAART impacts skin disease manifestations too
• Once the CD4disease occur

Sande The Medical Management of AIDS, 6th ed.
1999. p185.
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J Am Acad Dermatol 200654581-8.
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Keyword search Painful pruritic rash

• Chicken pox/varicella
• Vasculitis
• Syphilis
• Toxic Epidermal Necrolysis
• Eosinophilic neuritis/panniculutis

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Keyword Search Polymorphic Rash

• Kawasaki disease
• Polymorphic eruption of pregnancy
• Light polymorphic eruption
• Acute Generalized Exanthematic Pustulosis
• Varicella Zoster Virus
• Graft versus host disease
• Syphilis

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Multi-System illnesses

• Vascular
• Infections
• Neoplasms
• Drugs/Toxins
• Inflammatory
• Congenital
• Auto-immune
• Trauma
• Endocrine/Metabolic

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A Broad Differential!

• Infections
• Viral (HIV, VZV, HSV, CMV, Parvo, small pox?)
• Bacterial (Staph, GAS, Disseminated GC, Syphilis,
  Bacillary Angiomatosis)
• Fungal (Histo, Cocci)
• Neoplasms
• Mycosis Fungoides, KS, other
• Drugs/Toxins
• Cocaine
• Drug rash/TEN (no reported meds)
• Inflammatory/Auto-immune
• Vasculitis, SLE, Behcets, IBD, Kawasakis Disease

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Revised Problem List

• HIV/AIDS, low CD4 count, no Rx
• Fever
• Diffuse polymorphic rash with erythematous
  papules, pustules and necrosis
• Oral Ulcers
• Pyuria and WBC casts
• Daily Cocaine Use
• Multiple sex partners
• Arthralgias

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Acute Oral Ulcers
Bruce A.and Rogers R. Dermatologic Clinics.
2003211-15.
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Bruce A.and Rogers R. Dermatologic Clinics.
2003211-15.
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Bruce A.and Rogers R. Dermatologic Clinics.
2003211-15.
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Revised Problem List

• HIV/AIDS, low CD4 count, no Rx
• Fever
• Diffuse polymorphic rash with erythematous
  papules, pustules and necrosis
• Oral Ulcers
• Pyuria and WBC casts
• Daily Cocaine Use
• Multiple sex partners
• Arthralgias

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Urinary Casts and Associated Pathologic
Conditions
Adapted from Simerville JA. Am Fam Phys Mar
2005 71(6) 1153-62
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Keyword Search Rash and Pyuria

• Kawasaki Disease
• Allergic Interstitial Nephritis
• Toxic Shock Syndrome

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Revised Problem List

• HIV/AIDS, low CD4 count, no Rx
• Fever
• Diffuse polymorphic rash with erythematous
  papules, pustules and necrosis
• Oral Ulcers
• Pyuria and WBC casts
• Daily Cocaine Use
• Multiple sex partners
• Arthralgias

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Keyword Search Cocaine and Rash

• Cocaine induced Churg-Strauss (vasculitis)

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A Broad Differential!

• Infections
• Viral (HIV, VZV, HSV, CMV, Parvo, small pox?)
• Bacterial (Staph, GAS, Disseminated GC, Syphilis,
  Bacillary Angiomatosis)
• Fungal (Histo, Cocci)
• Neoplasms
• Mycosis Fungoides, KS, other
• Drugs/Toxins
• Cocaine
• Drug rash/TEN (no reported meds)
• Inflammatory/Auto-immune
• Vasculitis, SLE, Behcets, IBD, Kawasakis Disease

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Final Candidates

• Lupus or vasculitis
• Disseminated Histoplasmosis
• Disseminated HSV
• Disseminated VZV
• Disseminated Gonococcus
• Botryomycosis
• Kawasakis Disease
• Behcets
• Secondary Syphilis

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Disseminated Histoplasmosis

• Pros
• Advanced HIV
• Diffuse rash
• Oral Ulcers
• Fever and systemic sxs

• Cons
• Lack of liver or splenic involvement
• Lack of bone marrow involvement

In one series of AIDS patients, the most common
manifestations of disseminated histoplasmosis
included fever, weight loss, splenomegaly and
hematologic abnormalities
Int J Derm 200140518-521.
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Disseminated HSV

• Pros
• Polymorphic rash
• Vesicular and ulcerative lesions
• Oral ulcers
• High risk sexual behavior
• HIV

• Cons
• Disseminated disease rare in HIV
• Much more likely to have chronic ulcers
• Primary infection uncommon in HIVmost have
  reactivation
• Grouped vesicles typical rash

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Disseminated VZV

• Pros
• Polymorphic rash
• Atypical generalized zoster (rare but not
  primary)
• Vesicular and ulcerative lesions
• Oral ulcers

• Cons
• Prior infection as a child rules out primary
  infection
• Reactivation usually confined to dermatome(s)

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Disseminated Gonococcus

• Pros
• High risk sexual behavior
• Fever
• Skin lesions
• Arthralgias
• Oral ulcers
• Disseminationmore common in women

• Cons
• Absence of tenosynovitis
• Rash involves extensor surfaces of hands and
  dorsal surfaces of ankles/toes

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Botryomycosis

• Pros
• Diffuse skin lesions with pustules and ulceration
  
• Dissemination associcated with immuno-compromise

• Cons
• No known trauma
• No purulence evident
• Lesions diffuse, no focal source

Botromycosis a rare infectious disease most
commonly involving the skin and often following
trauma or foreign bodies. The skin lesions are
typicallly scattered papular and nodular lesions
that demonstrate purulent secretions. Staph
aureus is the most common cause.
JEADV 20031787-90.
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Behcets Disease

• Pros
• Polymorphic rash
• Cutaneous pustular vasculitis
• Oral ulcers
• Arthralgias
• Pyuria
• Fever and systemic sxs

• Cons
• Oral ulcers are recurrent
• No genital ulcers
• No eye or CNS involvement
• Rare

Dermatology Clinics 20032141-48.
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Clinical Infectious Diseases. 200132
1628-1634.
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Kawasakis Diagnostic Criteria

• History of fever of 5 days duration
• Plus 4 of the 5 associated physical findings
• bilateral nonpurulent conjunctivitis
• changes of the oropharynx, including injected
  pharynx, injected and/or dry fissured lips,
  and/or a strawberry tongue
• changes of the peripheral extremities, including
  edema and/or erythema of the hands and the feet
  (usually followed by desquamation)
• a polymorphous, erythematous, nonvesicular
  exanthem
• cervical lymphadenopathy (LNs 1.5 cm)
• In addition to the above criteria, results of
  evaluation for other infectious or noninfectious
  causes must be negative.

Clinical Infectious Diseases. 200132
1628-1634.
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Kawasakis Disease

• Pros
• Polymorphic rash
• Oral lesions
• Arthralgias
• Pyuria
• Fever and systemic sxs
• HIV increases risk??

• Cons
• No cervical adenopathy
• No hand/foot swelling
• Skin rash in our patient dissimilar
• Rare

Clinical Infectious Diseases 2001321628-34...
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Syphilis Background

• Caused by spirochete T. pallidum
• Recent increases in infection rates
• Common co-infection with HIV
• Stages
• Primary genital chancre
• Secondary 3-6 weeks later
• Non specific fever, malaise, myalgias, rash
• Specific mucosal lesions, condyloma lata,
  alopecia, LAN
• Rarer iritis, uveitis, arthritis, GN, nephritic
  syndrome
• Late or tertiary

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The polymorphism of secondary syphilids depends
entirely on the degree of inflammatory infiltrate
and the level of vascular involvement and the
resulting ischemia of the skin.
Clinics in Dermatology 200523555-564
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Lues Maligna

• Ulceronodular syphilis
• Rare ulcerative variant of secondary syphilis
  (
• Pleomorphic lesions
• Significant constitutional sxs
• Strongly positive RPR
• Inflammatory infiltrate
• Responds rapidly to therapy
• Increased incidence in HIV era

Scandinavian Journal of Infectious Diseases 2005
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Secondary Syphilis

• Pros
• High risk sexual behavior
• Fever, arthralgias
• Polymorphic rash
• Oral Ulcers
• HIV
• Lesions on palms
• Pyuria (GN?)

• Cons
• Recent monogamy

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Final Diagnosis

• Secondary Syphilis
• Diagnostic Test
• Serology RPR/FTA
• Skin biopsy

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Selected References

• Berger T. Dermatologic Care of the AIDS Patient
  in Sande The Medical Management of AIDS, 6th
  ed. 1999. WB Saunders Co.
• Bruce A.and Rogers R. Acute Oral Ulcers.
  Dermatologic Clinics. 2003211-15.
• Dourmishev L and Dourmishev A. Syphilis Uncommon
  presentations in adults. Clinics in Dermatology
  200523555-564.
• DAmico R Zalusky R. A case of lues maligna in
  a patient with AIDS. Scan J of Inf Dis 2005
• Gnann J. VZV Atypical Presentations and
  Unusual Complications. J Inf Dis
  2002186(Suppl 1)S91-8.
• Johnson R et al. Kawasaki-Like Syndromes
  Associated with HIV Infection. Clinical
  Infectious Diseases. 200132 1628-1634.
• McCarty M et al. Complex Aphthosis and Behcets
  Disease. Dermatology Clinics 20032141-48
• Simerville JA et al. Urinalysis a comprehensive
  review. Am Fam Physician Mar 2005 71(6)
  1153-62.
• Up-To-Date. Online version 14.2. Numerous
  cards!
• ZancanaroP et al. Cutaneous manifestations of HIV
  in the era of HAART An institutional urban
  clinic experience. J Am Acad Dermatol
  200654581-8.