[CIS PIDD] [cis-pidd] 12 year old with frequently recurrent episodes of facial HSV-1

[Seppänen Mikko]

Dear Michael, 

yes, it would be a feature of DOCK8, as well as all the non-GATA2, non-NK deficiencies in the list I wrote. That she has no eosinophilia decreases the chance of finding DOCK8 a little, however I would probably start with that (and has to be searched for specifically, no NGS/WES technique detects it reliably). Especially if molluscum contagiosum or warts...

IgE might be clearly allergic (seen for example by microchip array testing) or less specifically elevated, but such information we might only have for STAT3 (low specific titers, diminished mast cell function, see recent article from NIH cohort), DOCK8 (high specific titers) and Netherton's (high specific titers)?

In almost all autoimmune immune deficiencies (often not emphasized, but see Verbsky, Chatila, Curr Opin Pediatr 25(6):708-, 2013 and its excellent Table 1) and hypomorphic SCIDs (see for example Liston A, Enders A, Siggs OM. Nat Rev Immunol. 2008 Jul;8(7):545-58 for general discussion). You also commonly seem to have high specific IgE titers as well as in CD3g def (which probably should be included in the group of AI PIDDs). So if You are looking for a known immune deficiency, these are Your choices based on severe atopy. 

If this is "just severe atopy" and herpes and familial seizures (that neurologists cannot explain) are the key clues, You might be looking at a novel TLR3-IFN pathway def, there are >50 genes in that pathway (see the article by Casanova's group on TLR3 immunity in "mice and men"). There is at least 1 report on TLR3 polymorhisms in severe eczema herpeticum. 
However, for "simply atopy" and eczema herpeticum, her disease course would be most severe indeed... and low NKs may not be coincidental....

We would probably all love to hear if You'll crack the case, I would at least.

Mikko Seppänen, 
Finland

-----Alkuperäinen viesti-----
Lähettäjä: michael clayton [mailto:mhclayton at msn.com] 
Lähetetty: 12. helmikuuta 2014 20:48
Vastaanottaja: CIS-PIDD
Aihe: Re: [cis-pidd] 12 year old with frequently recurrent episodes of facial HSV-1

Thanks to everyone for your suggestions.  The patient's IgE was 183.  No monocytopenia (absolute count is 700).  Normal lymphocyte response to Candida (as well as PHA, ConA, PWM).  I wasn't clear on Val dose- she is receiving 500 twice daily.  Will try pushing this higher/give more frequently.  Could this mild elevation in IgE be consistent with a DOCK 8 mutation?
Thanks,  Michael Clayton

On Feb 11, 2014, at 2:54 PM, Michi wrote:


> Strongly consider DOCK8!

> 

> Von meinem iPhone gesendet

> 

> Am 11.02.2014 um 21:49 schrieb michael clayton <mhclayton at msn.com>:

> 

> Dear Colleagues:  

> 

> I wonder if you could offer advice on treatment of a 12 year old girl who has had frequently recurrent episodes of facial HSV-1 (culture confirmed) over the past 8 months.  She typically has an outbreak over her right cheek with a sense of tinglng, pain and warmth preceding the outbreak of vessicles.  No systemic symptoms.  No eczema or skin trauma.  Frequency is about every 10-14 days, and the longest interval between outbreaks has been 3 weeks.  She occasionally has an outbreak over lateral arm on same side and more rarely, over the lower arm.  She is developing chronic skin changes at these sites with thickening, mild hyperpigmentation and persistant stinging between outbreaks.  Stress and menstrual periods obviously make the episodes more severe, but starting an OCP has had no significant effect, nor did use of a high SPF sunblock daily over these areas.    The primary care provider previously had her use a daily regimen of acyclovir 400 mg BID with valacyclovir added in at onset of rash (500 BID).  Topical antivirals were not helpful.  I changed her prophylactic regimen to daily valacyclovir, also with no benefit. 

> 

> Other health history:

> -Very atopic girl with multiple food sensitivities, both type I and II as well as environmental sensitivities.

> -Long standing (earliest childhood) history of potentially autoimmune problems including alopecia, granuloma annulare, recurrent episodes of urticaria, intermittent joint swelling and pain with normal ANA, RF

> -Suspected seizure activity with "drop attacks" associated with intense exercise, and emotional outbursts that are sustained and suggestive of a partial complex sz. disorder, but normal EEG and negative cardiac workup.  

> -Obstructive sleep apnea.

> -Asthma, step II well-controlled.

> -Menorrhagia.

> -Two outbreaks of varicella after receiving her varicella vaccine.

> 

> Family History:

> Younger brother with eczema and seizure disorder.  Mother has alopecia areata, Two maternal aunts have Crohn's disease, maternal grandmother has lupus.  Virtually all adult females on maternal side have hypothyroidism.

> No known immune deficiencies, or problems specifically with herpes or zoster.

> 

> Labs:

> Nl CBC with diff

> Immunoglobulins:  IgG 1230, IgA 138, IgM 229 (30-211)

> Tetanus IgG= 2.5

> Pneumococcal serotypes= 8/13 protective range

> CH50= nl.

> Immune deficiency panel (CD 16/56= 5%, absolute CD4= 1046, all others normal, as well)

> Lymphocyte mitogen response panel normal

> NK cytotoxicity profile at Mayo:  Diminished but not absent natural NK cell cytotoxicity which was comparable to shipping control.  Normal NK cell number (86 cells/ul.)

> Negative Celiac Panel.

> ANA, RF (-)

> 

> I plan to repeat the NK cytotoxicity panel, but wonder if anyone has other ideas regarding workup or treatment?  She is scheduled to see a Pediatric ID consultant within the month, and is followed by a Pediatric Rheumatologist without a diagnosis, thus far.  Thanks in advance,

> 

> Michael H. Clayton, MD, MPH

> Albuquerque, NM

> 505-228-7958

> mhclayton at msn.com

> 

> 

> 

> 

> 

> 

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