Pediatric News

Wednesday, March 19, 2008

Issue 3, March 2008

Welcome to the March 2008 issue of the Pediatric Unit newsletter. We will highlight a few interesting cases and present a review of epidermolysis bullosa.

We invite you to join us on May 3^rd, 2008 for a conference sponsored by our Gastroenterology Department: “Challenging Gastrointestinal Disorders Series: Eating Disorders and Obesity.” This symposium will provide insight into new therapies in the field of pediatric gastroenterology, feeding disorders, anorexia, and obesity. Leading experts will guide you in the diagnosis and management of anorexia nervosa, feeding the “difficult child,” the health impact of obesity, and trends in weight management programs. You can view our conference brochure or call 415-600-0743 for more information.

Please feel free to contact us with any comments or suggestions.

Your Editors,

Jennifer Do, MD (DoJH@sutterhealth.org)
Inessa Gofman, MD (gofmani@sutterhealth.org

Who Have We Been Admitting?

This past month continued to be busy both on the ward and in the intensive care unit. There were many patients with bronchiolitis and asthma. We also cared for children with ITP, DKA, Kawasaki’s disease, seizures, osteomyelitis and parapneumonic effusions.

Interesting Cases of the Month

A previously healthy 11-year old male presented to an outside emergency department with a one-day history of left inner thigh pain and fever up to 104.2F. He was noted to have leukocytosis and Staph Aureus (MSSA) bacteremia. We admitted him for further evaluation and management of osteomyelitis with myositis and fasciitis, a diagnosis which was later confirmed by MRI. Despite appropriate IV antibiotics, the patient developed hypotension, respiratory distress and a diffuse dermatitis. He was transferred to our PICU for inotropic support and management of DIC with multiorgan system involvement. The patient’s hospital course was complicated by the development of numerous septic pulmonary emboli with pneumatoceles and lower extremity DVT requiring anticoagulation with Lovenox. His clinical status slowly improved and he was discharged home to complete a six-week course of parenteral antibiotics. The patient had close follow-up with hematology, infectious disease, oOrthopedic surgery, pulmonology and physical therapy specialists.
A six-month old male infant presented with a two-month history of upper airway congestion and weight loss. He was noted to have two subcutaneous nodules on the right parietal and left occipital areas. The patient was seen by his pediatrician for a fever of 38.5. He also had nasal congestion, rhinorrhea, tachypnea and splenomegaly. He did not have lymphadenopathy or hypoxemia. His chest X-ray revealed increased interstitial markings. His laboratory studies were notable for a WBC of 68K, Hgb of 7, platelet count of 67K, PT 18, PTT 48, fibrinogen 110, and D-Dimers >10,000. Peripheral blood smear revealed 40% monocytes and 7% blasts. His RSV nasopharyngeal sample was positive. We admitted him to the hematology/oncology service for further evaluation and treatment of a possible leukemia with DIC and RSV pneumonia. The bone marrow aspirate showed 68% blasts (CD 68 positive, CD33 positive and MPO negative). A diagnosis of acute monocytic leukemia was made. The family consented to COG protocol AAML0531 for newly diagnosed AML. This unique protocol stratifies patients by risk and randomizes the patients to either receive or not to receive Gemtuzumab (an antibody against CD33 immature myeloid protein). Our patient did not have high-risk cytogenetics (Philadelphia chromosome, monosomy 5 or 7) or low risk molecular findings (TEL/AML or inv16). We therefore classified him as an intermediate risk. RSV infections in newly diagnosed infants with hematopoietic malignancies can progress to severe pneumonia and death. We therefore treated him with two doses of Palvizutimab and his RSV infection resolved. His DIC slowly improved with appropriate treatment. The patient tolerated first cycle of induction chemotherapy.
A previously healthy 13-year old female presented to an outside emergency department in shock after she was found unresponsive by her parents. The patient had a two-day history of fever, vomiting and watery diarrhea. She developed a diffuse erythematous rash on the day of admission. Further history revealed recent menses and a remaining fragment of a tampon was removed. The patient received aggressive IV fluid resuscitation, inotropic support and IV antibiotics, and was transferred to our PICU for further management of toxic shock syndrome. Although the patient’s blood cultures were negative, her vaginal culture was positive for penicillin and erythromycin resistant Staph Aureus. The patient was initially treated with Clindamycin and Nafcillin but developed a drug rash and was switched to Vancomycin. The patient completed a 10-day course of IV antibiotics and was discharged home with close follow-up with her primary care physician and the infectious diseases specialist.
A five-day old former 37-week premature male neonate developed blisters on his extremities. The blisters were noted on his third day of life. Cultures for herpes and bacteria were sent from an outside hospital. We admitted the patient for further evaluation and management of his vesicular lesions. The patient was clinically stable except for multiple bullae like blisters on his hands and feet. Formation of the bullae could be induced with rubbing of the skin. A few of the bullous lesions spontaneously ruptured, exposing the underlying dermis. The patient was afebrile and did not have any erythema, warmth, or induration of his skin lesions. Bacterial and viral skin cultures remained negative. We consulted Dermatology and a diagnosis of epidermolysis bullosa was made. The dermatologist recommended using Aquaphor or petroleum jelly along with Tefla and kerlex dressings. We discharged the patient home with close follow-up with his pediatrician and the dermatologist.

Review of the Month: Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of inherited skin disorders characterized by blister formation following mechanical trauma. EB can be classified as EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and hemidesmosomal EB (HEB). EBS is the mildest form whereas the other subtypes are associated with more severe extracutaneous involvement. There are an estimated 12,500 individuals affected with EBS in the United States. The National EB Registry reports a frequency of 50 cases per 1 million lives births. Approximately 92% of these cases are EBS, 5% are DEB, 1% are JEB, and 1% are HEB. Infancy is a critical period for EB patients as generalized blistering can lead to infection, sepsis, and death. The severe subtypes increase the infant mortality risk. The most common cause of death in EB patients who survive infancy is metastatic squamous cell carcinoma. This skin malignancy usually presents between the ages of 15-35 years in patients with recessively inherited EB.

EBS is characterized by intraepidermal blistering with minimal internal involvement. Mechanical trauma induces blister formation and the lesions generally heal without significant scarring. The mild form tends to occur on the palms and soles and is associated with hyperhidrosis. The severe form affects the hands, feet, and extremities. Associated findings include palmoplantar hyperkeratosis and erosions along with herpetiform blisters of the oral mucosa. Both dominant and recessive inheritance patterns have been observed in EBS.

JEB is characterized by intralamina lucida blistering. The lethal subtype of JEB presents with generalized blistering at birth. An absence or severe defect in the expression of laminin 5, an anchoring filament glycoprotein, is the basis of this disease. Findings include erosions around the eyes, nares, and mouth along with significant hypertrophic scarring. In addition, the conjunctival, corneal, oral, pharyngeal, esophageal, genitourinary, and rectal mucosae can also be involved. There is an increased risk of death from sepsis and these patients generally do not survive beyond infancy. The nonlethal form of JEB also presents with generalized blistering during infancy. In addition to periorificial erosions and hypertrophic scarring, scalp, nail, and dental abnormalities can also be found. Erosions of the mucous membranes can result in stricture formation.

DEB is caused by defective formation of the anchoring fibrils. Blister formation results in dystrophic scarring and milia formation. The dominant form of DEB presents with generalized blistering during infancy. As the patient ages, localized blistering occurs. There can also be involvement of the oral mucosa, dentition, and nails. The recessive subtype of DEB ranges from mild to severe in presentation. The mild, localized form involves nails and acral areas with minimal mucosal involvement. The severe, recessive form presents with extensive blistering and dystrophic scarring primarily on the acral surfaces. Flexion contractures of the extremities with resulting pseudosyndactyly (mitten-hand deformity) can be observed. Strictures and stenosis of the internal mucosae can lead to malabsorption, iron deficiency anemia, and failure to thrive. These individuals are at risk for development of squamous cell carcinoma in areas of chronic erosions.

HEB is associated with muscular dystrophy and pyloric atresia. HEB with muscular dystrophy is characterized by variable blister formation and dental abnormalities with later onset of muscular dystrophy. The severity of blistering activity does not correlate with the degree of muscular dystrophy. EB with pyloric atresia presents with congenital pyloric atresia and severe blistering. This subtype tends to be fatal during infancy due to the extensive internal mucosal involvement.

The evaluation of a patient with suspected EB includes a thorough physical examination and two skin biopsy specimens from fresh blisters for electron microscopy (EM) and immunofluorescent microscopy (IM). The EM can provide information about the level of skin separation and the basement membrane zone morphology. The IM offers additional information about the level of blistering and immunomapping with antibodies can elucidate a particular molecular defect. A CBC count with iron studies can evaluate for anemia in patients with severe EB, especially the recessive DEB subtype. Poorly healing wounds require appropriate bacterial and viral cultures and treatment of secondary infections. These patients are at risk for both Gram positive and Gram negative bacterial infections. A strict wound care regimen to prevent skin infections and sepsis is necessary. An upper GI series or endoscopy can evaluate for esophageal strictures or pyloric atresia. Supportive care for dysphagia and close monitoring for esophageal lesions are advised. Patients with severe esophageal strictures may require gastrostomy tube feedings for adequate nutrition and growth. The increased caloric and protein intake can aid wound healing and recovery. Surgical correction for flexion contractures, especially the mitten-hand deformity, can be challenging due to its high recurrence rate. Nighttime splinting of the interphalangeal spaces can delay the recurrence. Physical therapy can be helpful in maintaining range of motion and reducing extremity contractures. Careful screening for squamous cell carcinoma with surgical excision of these aggressive malignancies is needed. Cultured human keratinocytes have been used as short-term therapy for chronic, nonhealing wounds. These allografts produce cytokines that stimulate reepithelialization and wound healing but are eventually rejected by their immunocompetent hosts. Prenatal diagnosis of EB with either a chorionic villi sample at 10 weeks or an amniotic fluid sample in the second trimester can provide genetic counseling for affected families.

Pediatric Grand Rounds Schedule
Grand Rounds are held at Bothin Auditorium at the California Campus (3700 California Street) in San Francisco on Fridays at 9 a.m. unless indicated otherwise.

March 21, 2008
Pediatric Hand and Microsurgery
Kyle Bickel M.D.
The Hand Center of San Francisco

March 28, 2008
Department of Pediatrics Business Meeting

April 4, 2008
Pediatric GI Motility Disorders
Christine Nguyen M.D.

Pediatric Gastroenterology

Physician Foundation at California Pacific Medical Center

April 11, 2008
Methicillin-Resistant Staphylococcus Aureus
Ritu Bonerjee M.D., Ph.D.

Fellow, Pediatric Infectious Disease

University of California, San Francisco

April 18, 2008
Back Problems in Kids and Adolescents
Edward Sun, M.D.
Orthopedic Surgeon

April 25, 2008
Department of Pediatrics Business Meeting