Unusual skin changes in 4yearold SCID patient

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Unusual skin changes in 4-year-old SCID patient

• Edyta Heropolitanska-Pliszka
• Magdalena Kurenko-Deptuch
• Immunology Department
• Childrens Memorial Health Institute
• Warsaw Poland
• 
  
• 
  
  
  PRAGUE 2007

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Registry of PIDs in CMHI1980 2006 n
102129 SCID / 6 OS
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Cutaneous disorders in SCID patients

• Recurrent skin abscesses
• Extensive candidiasis in the mouth and diaper
  area may persist and involve the rest of the skin
• Intractable eczemalike dermatitis
• Severe seborrheic dermatitis over the scalp,
  ears, and nasolabial folds
• Impetigo and severe skin infections with deep
  ulcers in the perineum, tongue, and buccal mucosa
  
• Sparse hair and absence of the eyebrows and
  eyelashes
• Manifestations of graft-versus-host disease
  (GVHD) that ensue a few days to weeks after
  transfusion include
• in the acute setting a maculopapular or
  morbilliform rash with progress to erythroderma
  and exfoliative dermatitis
• in chronic GVHD lichenoid or sclerodermoid
  lesions

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Exfoliative erythrodermy in Omenn Syndrome
on CsA treatment
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Impetigo and severe skin infection
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Skin changes in BCG-itis
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Extensive fungal infection
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Extensive candidiasis
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Materno-fetal engraftment
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Acute GVHD after non-irradiated, non-filtrated
blood transfusion
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Chronic GVHD 150 days after HSCT
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4-year-old girl

• young, non-consanguinous parents
• healthy, elder brother,
• II-nd pregnancy, II-nd delivery after caesarean
  operation, b.w. 3030g
• vaccinated with BCG and hepatitis B after birth
• breast-fed for 16 months

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• 2 m.o. - dermatitis atopica
• 18 m.o. - pneumonitis, diarrhea, maculo-papular
  skin changes on extremities, lymphopenia (WBC
  9100 L-9)
• 20 m.o. - erosive stomatitis, failure to thrive,
  papulo-vescicular eruptions on extremities,
  lymphopenia (WBC 9300 L-14)
• DIAGNOSIS benign histiocytosis
• 21 m.o. - bronchitis obturativa, extensive oral
  thrush, failure to thrive, papulo-erthrodermatous
  eruptions on extremities, buttocks and face
• DIAGNOSIS lymphoma benignum cutis

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• 32 m.o. - bronchitis obturativa, uticaria
  pigmentosa , failure to thrive, normal
  immunoglobuline concentration (IgG-550 mg/dl)
• DIAGNOSIS mastocytosis
• 36 m.o. - bronchitis obturativa, failure to
  thrive, leukopenia with agranulocytosis (WBC
  2200 N-11)
• DIAGNOSIS systemic disease
• 40 m.o. admitted to Immunology Department CMHI
• failure to thrive, papulo-macular skin
  changes with small scales and scarring on
  extremities, buttoks, face, obturative
  bronchopneumonia
• DIAGNOSIS primary immunodeficiency disorder

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Basic blood tests

• GOT 42 U/l
• GPT 35 U/l
• CRP lt0,2 mg/dl
• LDH 265 U/l

• WBC - 5,4 K/ul
• N-77
• L-17
• E-3
• B-3
• RBC - 3,66 M/ul
• Hgb - 12,2 g/dl
• Plt - 260 K/ul

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Microbiological investigation

• Pneumocystis carini PCR in blood and BAL
  negative
• Mycoplasma sp., Chlamydia sp., Legionella sp.
  negative
• Mycobacterium tuberculosis PCR in BAL negative
• HIV-1 PCR negative
• HHV 6 PCR negative
• HSV DNA - negative
• HCMV PCR DNA in leukocytes and urine both
  positive
• Aspergillus sp. index ELISA (0,660) and PCR ()

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Humoral immunity

• IgG 1020 2013 mg/dl
• IgA 21 mg/dl
• IgM 147 mg/dl
• IgE 52 KU/L
• IgG1 990 mg/dl
• IgG2 lt11 mg/dl
• IgG3 16 mg/dl
• IgG4 lt0,4 mg/dl
• Monoclonal gammapathy IgG kappa
• Anty-HBs 0,0 after triple vaccination,
  anty-diphteria and anty-tetanus 0,0 after
  four-time-vaccination

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Cellular immunity

• CD45/SSC low 1517 kom/ul
• CD3/CD45 - 40,6 615 kom/ul
• CD3CD8/CD45 - 15,5 235 kom/ul
• CD3CD4/CD45 - 18,2 275 kom/ul
• CD1656/CD45 - 43,9 665 kom/ul
• CD19/CD45 - 10,5 160 kom/ul
• Control 117 /- 28
• PHA 675 /- 84
• CD3 2654 /- 370
• Chimerism VNTR no maternal engraftment

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Imaging studies

• USG - thymus present, no hepatosplenomegaly,
  lymphoadenopathy in nitch of liver and spleen
• Chest radiographs interstitial pneumonitis in
  both lungs
• CT scans enlarged lymph nodes in mediastinum
  interstitial infiltration with fibrous changes in
  both apexes
• HRCT permanent fibrous changes in both apexes
  enlarged lymph nodes in mediastinum

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Histologic findings

• BMA no signs of malignancy
• Skin biopsy
• - microscopy predominantly histiocytic
  infiltrates with lymphocytes present in the
  dermis and subcutaneous tissue with tendency to
  form granulomatous forms In T cell population
  predominance of T cytotoxic, less amount of T
  helper, the least of B cells
• - immunohistochemical reactions CD1a
  negative, CD68 positive (abundant reaction), Ki67
  and CD20 positive in small part of lymphocytes,
  CD3 positive in most lymphocytes.

DIAGNOSIS histiocytoma eruptivum generalisatum
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DIAGNOSIS

• OMENN SYNDROME
• T- B- NK SCID

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• Frozen skin biopsy PCR analysis of the T-cell
  receptor (TCR) genes
• analysis of TCRB / TCRG repertoire showed
  reproducible oligoclonal patterns with
  predominant clones shared between the two
  samples. It might reflect (antigen-driven?)
  selective outgrowth of T cells, which might be
  compatibile with an inflammatory reaction in the
  context of the presumed SCID syndrome
• 
  
  Thanks to Dr T. Langerak
• 
  Erasmus
  University

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Genetical diagnosis

• OMENN SYNDROME
• RAG-1/RAG-2 excluded
• Artemis excluded on the basis of low
  radiosensitivity
• IL7RA not tested
• Others ???
• Thanks to Prof. J.J. van Dongen
• Dr M. van der Burg

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Treatment

• antibacterial (PCP prophylaxis broad- spectrum
  antibiotics)
• antiviral agents (Gancyclovir)
• antifungal therapy (Amphomoronal, Worikonazol)
• IVIG every 7-10 days
• immunosupressive treatment (CsA,
• Encorton (1mg/kg.b.))

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HSCT

• March 2007 MUD PBPC
• Conditioning regimen (BuCyATG)
• Early outcome
• 10 day Engraftment Syndrome
• 15 day - good haematological reconstitution
• 20 day - GVHD II stage in skin (CsA,
  steroids)
• 27 day reactivation of HCMV infection
  (Gancyclovir, Foscarnet)
• 39 day - complete chimerism
• 75 day good condition, no infection, still
  skin changes, chimerism pending