Double negatives: Not unimportant

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Double negatives Not unimportant

• Brian Vickery, MD
• Yale University
• CIS PID School

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History of Present Illness

• 44 yo F referred to YNHH AI clinic from
  Dermatology for evaluation of unusual T-cell
  population rule-out ALPS
• UK, 1994 G1P0 rash
• Flat pruritic erythematous macules on buttocks,
  trunk, and extremities
• Worsened after birth
• Resolved within 2-3 months with topical and oral
  corticosteroids

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HPI, cont.

• UK, 1998 G3P1 similar rash during pregnancy
• Sx much more intense unresponsive to topical or
  oral corticosteroids
• Exfoliation, Staph aureus and fungal
  superinfection, alopecia totalis
• Royal Society of Dermatology, London
  Sulzberger-Garbe syndrome ? Prednisone
• 2002 Lymphopenia mollusca contagiosa developed
  on Imuran ? d/ced
• CD3 ?/? double negative T-cells discovered
  during workup for persistent lymphopenia

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Additional History

• Mucocutaneous HSV-1
• Onychomycosis
• Iritis, choroiditis, exudative scleritis
• Sacroileitis
• s/p HepB series x 3 without seroconversion
• Denies sinopulmonary, invasive, or opportunistic
  infections, chronic diarrhea, mucocutaneous
  candidiasis
• Meds Clobetasol occlusion BID, emollients
• FamHx Asian Indian/Russian Jewish, no immune
  problems
• SocHx psychotherapist, no HIV RF

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Physical Examination

• Remarkable for
• Palmar erythema with peeling cracking
• Yellowed, cracked, hypertrophied nailbeds on all
  fingers
• Diffuse crops of umbilicated fleshy papules on
  all extremities, trunk, and face
• Large areas of deep violaceous erythema with
  xerosis but no sign of superinfection
• No hepatosplenomegaly
• No lymphadenopathy

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Laboratory

• Absolute lymphocyte counts 1200-1400
• CD4 count 150-200
• T-cell phenotype, stable over several
  measurements
• 430 cells/uL (34) CD3 ?? CD2- CD4- CD8- CD5
  CD25 CD45RO HLADR-
• CD62L and CD45RA expression normal
• B / NK cells normal

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Laboratory, cont.

• Normal serum immunoglobulins
• HSV1 titer IgM and IgG
• Normal CH50
• HIV negative by ELISA and viral load
• Extensive rheumatologic workup negative
• T-cell receptors polyclonal by PCR using beta
  gamma primers
• Normal serum IFE

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Lymphocyte Stimulation

• Borderline response to PHA
• No response to tetanus
• Good response to PWM Candida

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?
?

• CENTRAL PERIPHERAL
• -Defective TCR -ALPS
• CD3 gamma -HIV
• pre-B chain -Mycosis Fungoides/CTCL
• -Defective cell death -Defective homeostasis
• Caspases Caspases
• -??? IL-7/IL-15/Memory
• -???

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Summary

• 13 year history of diffuse, pruritic, refractory
  eczematoid dermatitis
• Plan Dermatology followup, steroids, ?fingolomod
• Lymphopenia with evidence of impaired cellular
  immunity
• Plan IV cidofovir ? IFN-?
• Episcleritis, choroiditis, iritis
• Plan close Ophthalmology followup
• Unusual DNT cell population
• Plan enrollment in NIH caspase-8 study