[PAGID] Patient with lymphopenia

[dmvascon at usp.br]

Dear Jason

We have seen some patients with very similar clinical and  
immunological features. I agree with all the previous discussants and  
test also for ADA, PNP, MHC class II deficiency, CD25 and IL-2  
deficiencies. It is important to stress that CD25 and IL-2  
deficiencies usually present autoimmunity (as well as PNP  
deficiencies). Unfortunately we cannot diagnose p56lck deficiencies.  
Despite this investigation the majority of patients fall into the  
category of primary (or idiopathic) CD4 lymphocytopenia.
It is interesting that some patients present very low numbers of T  
cells but mild symptoms (HPV and Candida infections, p.ex). On the  
other hand, some patients present very severe infections such as  
disseminated histoplasmosis or cryptoccosis, CMV, multifocal  
progressive leukoencephalopathy etc., and also neoplastic diseases  
such as lymphomas (usually high grade, sometimes extranodal). These  
patients with more severe diseases evolve like "moderately severe CID"  
and are very difficult to manage.
We usually perform lymphoproliferation tests based on the number of  
lymphocytes with mitogens (PHA, anti-CD3 and PWM) and also antigens  
(usually Candida, PPD, tetanus toxoid, CMV and Toxoplasma), but we try  
to test for antigens that the patient had been previously immunized -  
by vaccination or natural infection). We also test for apoptosis of T  
cells and its subsets. As a group, there is a striking  
lymphoproliferative deficiency partially restored by the addition of  
IL-2 in vitro. Some patients' cells improve their response with the  
addition of IFN-alpha in vitro (a few patients with extensive HPV  
infection have been treated with IFN-alpha with moderate clinical  
improvement).

Good luck with your patient.

Best regards,

Dewton

Dewton de Moraes Vasconcelos, M.D.; Ph.D.
University of São Paulo School of Medicine

Citando "Jason Raasch, MD" <raas0027 at umn.edu>:


> Please offer your insight into this 53 year old woman with persistent

> verruca plantaris (plantar warts) and severe lymphopenia.  Consider the

> following questions as you review the case:

>

>

>

> First note flow cytometry (presented in absolute numbers, gated on CD45):

>

>

>

> Total CD3 lymphocytes: 53 per mm3 (reference 1064-1672)

>

> CD3+CD4+: 10 (627-1102)

>

> CD3+CD8+: 38 (247-741)

>

> CD4:CD8 = 0.27

>

> CD19:  93 (95-418)

>

> CD56+16+: 93 (95-494)

>

>

>

> At first glance, whether primary or acquired, this is striking.  Now

> consider her clinical history:  She was well from birth through adolescence.

> Varicella at age five; shingles at age 19.  Seizures at age 23; on

> Phenobarbital for 10 years this was then discontinued and she has had no

> further neurologic events.

>

>

>

> By her late 20's she began having persistent verruca vulgaris on hands,

> knees, pre-tibial area and feet.  Over the last 30 years has failed OTC

> therapies as well as excision, laser ablation, cryotherapy, topical and oral

> retinoids and localized bleomycin.

>

>

>

> Variably positive ANA (up to 1:320, but often undetectable) starting in her

> 30s.  Other than intermittent arthralgias, no other symptoms.

> Hypothyroidism diagnosed at age 51 (thyroglobulin and thyroperoxidase

> antibodies undetectable).

>

>

>

> Lymphopenia brought to her attention at age 52 (WBC 4,000/mm3; ANC=3,200;

> ALC=240).  Medical record review actually demonstrates same findings as far

> back as 1970's and persistently each decade thereafter, suggesting a

> long-standing finding.

>

>

>

> Review of systems completely unremarkable except for the above, as well as

> mild depression and hypothyroidism.  No GI symptoms.  No history of

> recurrent infection.  No history of heart disease or abnormal facies.

> Patient reports unremarkable family history.

>

>

>

> Over the last 18 months the following have been UNREMARKABLE: electrolytes,

> ALT/AST, serum albumin and protein, B12, folate and iron levels, serum

> electrophoresis/immunofixation, quantitative immunoglobulins,

> tetanus/diphtheria, pneumococcal and varicella titers, isohemagglutinins,

> rheumatoid factor, dsDNA, CCP antibody, CRP, ESR, C3, C4, CH50, TSH and T4.

> Stool alpha-1 antitrypsin normal.  HIV ELISA X 2 negative.  FANA 1:40 with

> homogeneous pattern.

>

>

>

> INTERESTINGLY, this patient reports that her HEALTHY adolescent daughter was

> incidentally found to have just as severe a lymphopenia AND neutropenia.

>

>

>

> In summary this is a fairly health woman with a striking lymphopenia (that

> most likely has been present over the last 30+ years), persistent verruca

> vulgaris and intermittently positive ANA.  A HEALTHY daughter has

> lymphopenia and neutropenia and has not had evaluation.

>

>

>

> So the questions:

>

> 1.	Who has seen cases like this?

> 2.	Why has she had such a benign course despite such a lymphopenia?

> 3.	To what extent should a diagnosis be pursued?  In her daughter?

>

>

>

> I am interested in any comments.

>

>

>

> Have a great week.

>

>

>

> --jason

>

>

>

> Jason P. Raasch, MD

>

> Children's Hospitals and Clinics of Minnesota

>

>

>

> Midwest Immunology Clinic

>

> 2805 Campus Dr, #215

>

> Plymouth, MN 55441

>

>

>

> Telephone: 763.577.0008

>

> FAX: 763.577.0192

>

> e-mail: raas0027 at umn.edu

>

>

>

>



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