Hyperimmunoglobulin E Syndrome Presenting as Osteogenesis Imperfecta in a 3 Year Old Child
A three and a half year old boy was referred to Pediatric Infectious Disease clinic with a history of asthma, environmental allergies, multiple lung infections, long bone fractures, and hand-foot-mouth disease, for evaluation of recurrent skin abscesses and bullae. By the time of evaluation in Pediatric Infectious Disease Clinic a, referral to genetics had already been initiated to evaluate the child for Osteogenesis Imperfecta because of the history of recurrent long bone fractures.\nAccording to the patient’s mother, the abscesses and bullae usually occurred on the face and were generally of rapid onset. Most often, they began as a pimple on the cheek in the morning and progress forming large mildly erythematous bullae by the afternoon. Multiple lesions had been lanced and cultured, most often revealing Staphylococcal species. The mother first noticed very bad lesions on the patient’s face as a small infant, initially attributing these lesions to bad baby acne; however, the complexion was much worse than her other children, as well as other children who she knew. Additionally, the patient also experienced multiple, severe blisters over the leg when a cast was removed due to a distal tibia fracture. Additionally, approximately one and a half months prior to evaluation the patient was admitted to an outside hospital for recurring bullae on the medial aspect of the left foot. These bullae were surgically debrided and the fluid expressed was cultured, revealing budding yeast. The patient had a similar infection when he was three years old. At that time a culture from the lesion revealed yeast and the patient improved with oral fluconazole.\nThe patient was the product of a 37 week 2 day uncomplicated pregnancy, but was hospitalized in the NICU for ten days, requiring mechanical ventilation secondary to pulmonary edema.\nA review of the patients past medical history revealed a combination left tibia and fibula fractures at age 21 months, a combination left radius and ulna fracture at 29 months, and a fracture of the left tibia at 41 months. Each instance was due to minor trauma.\nLaboratory studies obtained from the outside hospitalization revealed a white blood cell count of 11.4 cell/cm, hemoglobin of 12.0 g/dL, and platelets of 385,000 cell/cm. The differential demonstrated 52% lymphocytes, 5% monocytes, 11% eosinophils, 31% neutrophils, and 1% basophils. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were both normal. A biopsy of the debrided tissue on his left foot revealed dermal changes consistent with a hypersensitivity reaction to a fungal infection. Direct immunofluorescence shows weakly patchy granular dermal-epithelial junction of IgM and C3.\nThe lesions responded to intravenous ambisome followed by Itraconazole. The subtyping of IgG were within normal limits, IgG1 of 894 mg/dL, IgG2 of 164 mg/dL, IgG3 of 17 mg/dL, and IgG4 of 133 mg/dL, with a normal antibody response to the Diptheria toxoid and Tetanus toxoid and T and B cell subtypes were normal.\nPartial immunizations had been given to date and the patient history revealed allergies to sulfa drugs, eggs, and some wheat products by skin test. His family history was significant for a paternal grandmother with CVID and asthma, asthma and allergies on the paternal side, and the patient’s mother and maternal grandmother had systemic lupus.\nOn physical exam, in Pediatric Infectious Disease Clinic at the University of Michigan, the height was in the 89th percentile, the weight is in the 96th percentile, and he appeared as a playful young boy in no apparent distress. There were multiple small, non-erythematous, hard papules over the cheeks and bridge of his nose. The facies were not dimorphic and the dentition was good. No blue tint of hue was noted in the sclera and the pupils were equal round and reactive to light. There was no cervical lymphadenopathy with no other masses in the neck were appreciated. The lungs were clear to auscultation bilaterally. The abdomen was soft, non-tender, non-distended with no hepatosplenomegaly. The medial aspect of the left foot had new granulation tissue with a lesion approximately 3 cm by 4 cm from a previous bulla. New bullae formation was occurring on the periphery of the healing lesion. Muscle mass, strength and tone were within normal limits and the joints were not hyper-extensible. The neurologic exam was grossly intact.\nLaboratory studies obtained from Pediatric Infectious Disease Clinic revealed an immunoglobulin panel with an IgA level of 214 mg/dL (normal 15-160 mg/dL), IgG level of 1260 mg/dL (normal 405-1160 mg/dL), IgM level of 117 mg/dL (normal 40-190 mg/dL), and an IgE level of >10,000 kU/L (normal 0-150 kU/L). The subtyping of IgG were within normal limits, IgG1 of 947 mg/dL, IgG2 of 92 mg/dL, IgG3 of 18.3 mg/dL, and IgG4 of 42 mg/dL, with a normal antibody response to the Rubella. A CH50 level was normal at 101 units (normal 52-128 units). The ESR and CRP were normal and a Gram stain and culture from the left foot were negative.