Age: 1.5
Sex: F
Vaccine: VARCEL
Symptoms: Antimicrobial susceptibility test resistant, Blood pressure, Culture negative, Death, Developmental delay
Clinical narrative: It was reported in a published article, title as stated above, that an 18 month old female with medical history significant for preterm delivery at 32 weeks' gestation via cesarean section, secondary to maternal prolactinoma and polyhydramios. At birth she was noted to have choanal atresia and a patent ductus arteriosus; a choroid plexus cyst was also noted on computed tomography of the head, and bilateral renal calculi were seen on ultrasound. The result of prenatal testing of the patient's mother for HIV antibody was negative, and the result of testing of the patient for HIV antibody as part of the state's newborn screening program was also negative. In the early postnatal period she required both a traceheostomy and gastrostomy-tube placement. Although her anomalies suggested a congenital syndrome, a specific diagnosis was not established at birth or through subsequent investigation. The finding of persistent lymphopenia on serial lymphocyte count and the absence of a thymic shadow on chest radiograph raised the suspicion of DiGeorge anomaly, but results of a fluorescent in situ hybrization study to detect the 22q11.2 deletion were negative. However, initial determination of lymphocyte subsets revealed severe depletion of both CD4 and, particularly, CD8 subsets, with normal or increased B cells (CD19) and natural killer cells (CD56). Lymphocyte-proliferation assays also revealed absent proliferation to standard mitogens. That trend would persist, albeit with some normalization of CD4 percentage, until the admission. In additional to her deficits in cellular immunity, the patient also had severe humoral dysregulation. Although her immunoglobuin (Ig)G, IgM, and IgA concentrations were within normal limits for her age, she failed to produce protective antibody titers to tetanus toxoid and Haemophilus influenza type B after immunization. Further workup of her immunodeficiency included testing for genotypes of severe combined immunodeficiency, such as ZAP-70 deficiency and associated promoter mutations, all of which were unremarkable. Because of the nursing care her tracheostomy required, she was placed in a chronic care facility. The patient had been hospitalized multiple times. During several admissions for exacerbations of chronic reactive airway disease, test results of nasopharyngeal aspirates were positive for respiratory syncytial virus. On 1 of those admissions, at 9 months of age, the patient suffered an exacerbation of her chronic ichthyosiform rash that was manifested by diffuse erythroderma, alopecia, and electrolyte disturbances. Quantitative Igs at that time revealed markedly elevated serum IgE (36000 IU); however her clinical course was not felt to be compatible with Job syndrome because of absent history of deep organ abscess. A diagnosis of Netherton syndrome was considered but not supported by the results of skin biopsy and hair-shaft examination. Furthermore, molecular testing results were negative for mutation on SPINKS. The diagnosis of Omenn syndrome was also considered, but testing for RAG1 and RAG2 was not performed. Despite the gastrostomy tube, she continued to suffer from failure to thrive and weighed only 8.6 kg at 18 months of age, with profound developmental delay. No cause for her immunodeficiency was ever elucidated, but because of this condition, her physician advised that she receive no live vaccines. Nevertheless, 5 weeks before her admission she was vaccinated with Varivax (Oka/Merck). The patient was admitted with a 4-day history of fever and increasing numbers of papulovesicular/pustular skin lesions. The rash was first noted on the patient's trunk 6 days before admission when she began having intermittent fevers. At that time, she was seen by her primary physician as an outpatient and evaluated by a pediatric dermatologist. Since that time, the lesions had become generalized, and on admission they covered her entire body including her scalp, palms, and soles. A culture from blood drawn 4 days before admission did not grow any bacteria, but a culture from 1 of the pustules revealed infection with methicillin-resistant Staphylococcus aureus. Three days before admission, she was started on benzathine penicillin and erythromycin, but the rash continued to progress. On the evening before the admission she was brought to the emergency department because of a fever of 103F. On admission the patient was awake, alert, responsive, and moving all extremities. She was afebrile but hypertensive, tachycardic, and tachypneic and had a blood pressure of 120/80 mm Hg, a heart rate of 150 beats per minute, and respiratory rate of 45/minute on 28% O2 via a tracheostomy collar. There were generalized erythematous-based vesicles and pustules, including on her palms, soles, scalp, and trunk, with the highest concentration being in the genital area. Her breath sounds were coarse, with occasional wheezes; her liver was palpable 3 cm below the costal margin, but laboratory testing on admission revealed a normal complete blood count, chemistry, and liver function. The patient was admitted with a preliminary diagnosis of staphylococcal pustulosis, but because of the mixed nature of the lesions and the history of varicella immunization, treatment was begun with intravenous vancomycin, intravenous ceftriaxone, and intravenous acyclovir. A 3-mm punch biopsy was performed by the pediatric dermatology service, 2 vesicles on the dorsum of the left foot were unroofed for bacterial, fungal, and viral cultures, and a Tzanck smear was obtain; the results of these tests were negative. On hospital day 4, fluid obtained from 1 of the vesicles was sent for diagnostic polymerase chain reaction and viral strain determination. New lesions continued to appear for >1 week, for a total of >14 days after initial appearance of the rash, and the patient continued to have low-grade fevers and mild respiratory distress. A chest radiograph on hospital day 4 revealed bilateral patchy consolidation. Two punched-out ulcers appeared on her left flank and another on her left frontal scalp; all 3 were >1 cm in diameter and surrounded by 3 to 4 cm of erythema and induration. On hospital day 4, the pathology report on the biopsy reported results consistent with a herpesvirus infection, although differentiation between herpes simplex virus and varicella zoster virus (VZV) was not possible. On the 4th day hospital day, the PCR was reported positive for vaccine-strain (Oka) varicella. After the 9th hospital day, new lesions gradually diminished, and by the 17th hospital day, the punched-out ulcers began to fill with granulation tissue. Although the patient's hospital course was complicated by S. aureus bacteremia and candidemia, as well as methicillin-resistant S. aureus superinfection of the primary lesions, her varicella continued to improve after this point. After a lengthy and difficult hospital course, she was discharged back to her chronic care facility on the 55th hospital day. The patient was subsequently readmitted on several occasions for ulcerated skin lesions and respiratory illness. VZV was never isolated from any specimen. Her lymphocyte-proliferation responses remained severely depressed, and she eventually died at 2 years, 2 months of age from respiratory failure. Additional information has been requested. A copy of the published article is attached as further documentation of the patient's experience.