Sex: U
Vaccine: MMR, VARCEL
Symptoms: Contraindicated product administered
Clinical narrative: Patient with DiGeorge anomaly (DGA) received the live measles mumps rubella and the varicella vaccine.;   This literature marketed report has been received from the authors of a published literature article, titled as stated above, concerning a child patient of a diabetic mother. The newborn screening panel showed T cell receptor rearrangement excision circles (TRECs) of less than 200 per cubic millimeter (mm3). Flow cytometry at two weeks of age was notable for lymphopenia with normal numbers of B lymphocytes and natural killer (NK) cells but absent naive T lymphocytes. No thymus tissue was identified on ultrasound of the left chest. This patient did not have a cardiac defect. Hypocalcemia was detected at day of life 18, at which point the infant was started on calcium supplementation. The diagnosis of complete DiGeorge anomaly (cDGA) was made at this time. Intravenous (IV) immunoglobulin replacement therapy and trimethoprim-sulfamethoxazole prophylaxis were initiated in the first 2 months of life. At 3 months of age, the patient developed diarrhea, an erythematous total body rash, alopecia, and eosinophilia. Histological examination of a skin biopsy demonstrated mild intercellular edema in the epidermis and a superficial perivascular lymphocytic infiltrate most of which consisted of cluster of differentiation (CD) 3+CD4+ T cells. Flow cytometry at this time showed increased numbers of T cells, 10 months pre-implantation. A molecular clonality analysis of the T cell receptor Vbeta genes detected T cell clones. The patient was diagnosed with atypical cDGA and started on cyclosporine as treatment for rash related to the oligoclonal T cells. Consistent with the diagnosis of cDGA, patient developed multiple infections in the first year of life including rotavirus gastroenteritis, Escherichia coli urinary tract infection, and Enterococcus faecalis wound and bloodstream infections. The patient was transferred to our facility for cultured thymus tissue implantation (CTTI) at eight months of age. After stabilization of patient 1 with gastrostomy tube placement and subsequent weight gain, the patient was given CTTI at 13 months of life with pre-CTTI methylprednisolone and rabbit anti-thymocyte globulin. In the week following CTTI, the patient was intermittently febrile with a maximum temperature of 38.9 Degree Celsius. Although one blood culture grew Candida albicans, subsequent cultures did not, and computed tomography (CT) of the chest and abdomen showed no evidence for fungal disease. Fevers resolved after empiric fluconazole therapy. Two months after transplantation, the patient again had high fevers without localizing source. Blood cultures were negative, but serum B-D-glucan, a marker associated with fungal infection, was positive. Given concern for possible Candida infection, the patient was treated with intravenous fluconazole for one month, followed by oral fluconazole prophylaxis. Despite fungal prophylaxis, one month later (3 months post CTTI), the patient was again admitted to the hospital for high fevers associated with cough and tachypnea. The patient had a newly enlarged right occipital lymph node. A chest CT was notable for mediastinal lymphadenopathy and right posterior apical lung consolidation. Over the ensuing ten days the patient continued to have high fevers despite broad-spectrum antibiotics. A repeat chest CT showed new airspace opacities. An open thoracotomy and lung biopsies of the right apex and right middle lobe revealed granulomatous lesions with numerous acid-fast bacilli. Mycobacterial cultures from the right middle lung nodule subsequently confirmed the presence of Mycobacterium avium complex (MAC). Antimycobacterial therapy was initiated with enteral clarithromycin, rifampin, and ethambutol. The patient developed right middle lung lobe collapse five months after CTTI. Bronchoscopy found a hard, plastic-like plug of the right middle bronchus that was unable to be removed. This persisted despite aggressive chest physiotherapy and airway clearance measures. The patient ultimately required rigid bronchoscopy to remove the hard plug. Though largely asymptomatic, chest imaging continued to show multifocal airspace disease and right middle lobe consolidation. Two months later, the patient underwent left occipital lymph node excision and repeat bronchoscopy. Bronchoscopy revealed a sessile bronchial mass, which was removed by laser. Cultures from both the excised lymph node and the bronchial mass grew MAC. While on antimycobacterial therapy, the patient had chronic diarrhea and poor weight gain. There was concern that the persistent mycobacterial disease was due to poor enteral absorption of medications. A central line was placed nine months post-CTTI for parenteral azithromycin, rifampin, ciprofloxacin, and amikacin. The patient was started on total parenteral nutrition. The patient then demonstrated consistent weight gain, resolution of diarrhea, and improvement in pulmonary disease. Nineteen months post-CTTI, the patient resumed enteral medical therapy with clarithromycin, rifampicin, and ethambutol. Clarithromycin was later changed to levofloxacin due to concern for ototoxicity. By 30 months post-CTTI, chest imaging and physical exam had improved, and the patient had good T cell reconstitution and function. Antimycobacterial therapy was discontinued after 25 months of therapy. The patient has been off mycobacterial medications for over 5 years with no sign of recurrence. The protracted illness with Mycobacterium avium complex did not appear to hinder cultured thymus tissue engraftment. Biopsy of the cultured thymus tissue allograft 2 months after implantation showed thymopoiesis. Naive T cells began to appear six months after implantation, and the naive CD4 T cells were within the normal range by 21 months post-CTTI.  On an unknown date (also reported as 4.5 years after CTTI), the patient was vaccinated with measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (M-M-R II) and on unknown date (also reported as six months later), the patient was vaccinated with varicella virus vaccine live (oka/merck) (VARIVAX) injection, both vaccines administered for prophylaxis (strengths, doses, lot #s, expiry dates and routes of administration were not provided) (contraindicated product administered).    This is one of the two cases received from the same literature article.  A copy of the published article is attached as further documentation of the patient's experience.; Sender's Comments:  US-009507513-2304USA007196: