[CIS-PAGID] 15 year old with antibody deficiency and atypical infection?

[Dimitriades, Victoria R.]

Dear Colleagues,

 

Please excuse the length of this e-mail, but I have a complicated patient for whom diagnosis and treatment suggestions would be appreciated:

 

15 year old female first seen 2.5 years ago with issues of recurrent sinopulmonary infections. She was found to have normal IgG, IgA, and low IgM and IgG2. Pneumococcal titers were protective in 1/14 serotypes after both conjugated and polysaccharide pneumococcal vaccines. Tet/Dip/ H.flu responses were adequate. Lymphocyte subpopulations were remarkable for a CD4 of 410. Mitogens and antigens were normal and Memory B cells were low. Of note, an IgE was elevated at 4430 with mild sensitization (skin prick and in vitro) to dust mite and grasses. 

CT scan showed mild fusiform bronchiectasis in one area. She was started on IVIg at around 700mg/kg and Bactrim prophylaxis and did well for 2 years with occasional break-through otitis or sinusitis.

 

During this time, a follow-up CT showed 2 new areas of nodularity (1-2cm) in L lower lobe described as granulomas. Bronchoscopy done at that time was unremarkable with negative AFB, no fungal or viral growth, and negative Aspergillus testing by IgG, precipitins, and complement fixation. We monitored these lesions over the next few months and decided, once they had enlarged (up to 7cm, rapidly) to start Voriconazole and obtain a needle biopsy. The biopsy showed necrotic inflammatory cells with coagulation necrosis. AFB, PAS, GMS stains showed no organisms. The remainder of the lung is completely normal.

 

After six weeks of treatment with further enlargement of lesions, testing was done: 

PPD- neg, HIV PCR- neg, 

Dihydrorotamine- normal, IFN-gamma  receptor present on T cells and monocytes,

ACE level- normal, Beta-D-glucan- 48 [>60], Galactomannans 0.475  [>0.5], 

STAT3- negative (HIgE scoring was 36, based mostly on IgE, pneumonias in past, and bronchiectasis)

 

We assumed Aspergillus based on the galactomannans drawn while on treatment, but lesions remain intermediate in their response despite adequate Voriconazole levels (some shrinking, others developing central necrosis and enlarging). We are planning open biopsy at this point for definitive diagnosis. I must also state at this time, since the discover of these lesions, this patient has remained completely asymptomatic, without shortness of breath, cough, or sputum. Her lung function is maintained and she participates in sports 3 days per week.

 

My question now is to your thoughts on diagnosis-- CVID variant with low CD4 predisposing her to atypical infections? Some form of Hyper IgE? Given the possibilities of these diagnoses, is there something we should be looking for in the biopsy or bloodwork to better help us treat?

 

Thank you for your time...

 
Victoria Dimitriades, MD
Assistant Professor of Pediatrics
Divisions of Allergy/Immunology and Rheumatology
Louisiana State University Health Sciences Center
Children's Hospital of New Orleans
200 Henry Clay Ave
New Orleans, LA 70118
(504) 896-9589 (A/I)
(504) 896-9385 (Rheum)
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