[CIS PIDD] 17 year old with CMCC, Crohn's Disease

[M CLAYTON]

Dear Colleagues, I welcome your thoughts on the following patient:
 
17  year old male of mixed Hispanic (mother) and Syrian (father) ancestry ,  delivered at 34 weeks gestation. Pregnancy was complicated by polyhydramnios.  He was admitted to the NICU with respiratory failure, and his course there complicated by recurrent pneumonias, GERD, hypothyroidism, poor feeding with G-tube dependency and a congenital myopathy. He was sent home with a ventilator which he has used ever since.  By two years he had recurrent, severe oral candidiasis as well as tinea corporis,  requiring frequent treatments with oral and iv antifungal agents.   Mitogen proliferation studies at an early age showed no response to Candida, normal proliferation to other antigens and negative evaluation for AIRE mutation.   Bronchiectasis was noted.  This pattern continued over the next several years with diarrhea and poor weight gain continuing.  Lymphocyte phenotyping showed low NK cell numbers, but normal CD4 count.  NK function very low.   IgG, IgM and IgE within normal range.  IgA slightly decreased.  He had fluctuating ANA titers as high as 640. 
 
Later, he was seen by an another immunologist and had an extensive workup which included B cell studies showing a decrease in total memory B cells and in class switched memory B cells.  IgG was within the normal range (873), IgG subclasses showed an absence of IgG4, slightly decreased IgG2, but IgG1 and IgG3 WNL.  Tetanus titer protective, Pneumococcal serotypes showed 71% normal response after PV23, with immunity waning over an 18 mos. period to 42% protective titers.  He was again challenged with PV23, but showed very little response (hyporesponsive over such a short interval?).  These titers were repeated a third time 18 months later, and 13/14 were protective.  Various studies done including STAT1, STAT3,ICOS,TNFRSF13B, IPEX, all negative.  Treg subset immunophenotyping WNL. He showed decreased cytokine response to TLR1-2 and TLR3 stimulation and decreased induction of IL17 with stimulation.  He was diagnosed with CVID, and sc IgG started.  Indeed, he had fewer respiratory tract infections with this.  He seemed to achieve a new level of stability, but the diarrhea and candidiasis continued.
 
He was admitted to hospital 3 weeks ago with a severe  rash on his buttocks and scrotum which subsequently blistered.  He had a perianal fistula at the time of admission that was being managed as an outpatient.  He has since developed crops of bullae on his extremities which on biopsy showed linear IgG deposits.  Diarrhea worsened with blood in stool.  He has urinary retention.  the GI service thinks the biopsy and clinical picture are most consistent with Crohn's and are starting Inflixumab.  
 
Do any of you have other thoughts on further evaluation of this very complicated young man?  Thanks in advance,
 
MIchael H. Clayton, MD, MPH       
 		 	   		  
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