Index of Suspicion in the Nursery

A 2-week-old girl, who was born at term without complications, is brought to her primary pediatrician after developing diarrhea. According to the mother, she has been having increasingly frequent watery stools since yesterday. The pediatrician notes a small, 1-cm reddish-brown papule on the right deltoid area. This lesion is unchanged from the initial assessment of the girl in the newborn nursery. The infant is otherwise doing well and because she can tolerate oral hydration, she is sent home with instructions for oral rehydration.Two weeks later, the girl returns to the pediatrician's office because of recurrence of diarrhea. A chance finding during the physical examination helps to make the diagnosis.A term baby girl is born via cesarean section to a 31-year-old G2P1, now P2, woman. The cesarean section is performed because of failed induction. Results of the maternal medical history and all prenatal screening tests are negative. Maternal blood is A+ and antibody-negative. An older sibling had neonatal hyperbilirubinemia. At birth, the infant displays significant hypotonia and diminutive respiratory effort. Apgar scores are 7 and 9 at 1 and 5 minutes, respectively. Positive-pressure ventilation is applied for 30 seconds, at which point the infant cries spontaneously.The only finding of note on the newborn examination at approximately 5 hours after birth is mild facial icterus. At 9 hours after birth, the newborn's transcutaneous bilirubin (TcB) is 11.2 mg/dL (191.6 μmol/L). Because of this substantially elevated TcB value, a direct antiglobulin test (DAT), complete blood count (CBC) with differential count, total serum bilirubin (TsB), and blood type of the newborn are ordered. Triple phototherapy is initiated. The noteworthy laboratory findings include: blood type of O+, strongly positive (4+) DAT, hemoglobin of 13 g/dL (130 g/L), hematocrit of 37% (0.37), white blood cell count of 30×103/μL (30×109/L), 15% bands, reticulocyte count of 7.2% (0.72), lactate dehydrogenase of 1,039 units/L, and TsB of 14.5 mg/dL (248.0 μmol/L).After 6 hours of semi-continuous triple phototherapy, the TsB measures 15.6 mg/dL (266.8 μmol/L). Of note, interruptions in triple phototherapy are permitted for spontaneous breastfeeding on demand with a phototherapy blanket. At 18 hours after birth, the TsB reaches 16.1 mg/dL (275.4 μmol/L). Consequently, quadruple phototherapy is initiated, with expressed human milk fed via bottle. After 11 hours of intense continuous quadruple phototherapy, the TsB peaks at 16.4 mg/dL (280.5 μmol/L). Subsequently, the newborn is transferred to the neonatal intensive care unit.Due to the infant's rapidly progressive hyperbilirubinemia, additional blood testing is performed for minor blood group antigens.A 13-day-old previously healthy term infant is admitted to the hospital with left eye swelling (Fig. 1) present for 2 days. She was born via spontaneous vaginal delivery at 37 weeks' gestation to a G3P3 woman who had normal prenatal laboratory test results. The infant's birthweight was 2,675 g. Her newborn course was uncomplicated and she was discharged on postnatal day 2. Ten days later, the infant was evaluated by her primary practitioner for mild left eye swelling and slight injection of her conjunctiva. She was given erythromycin ointment for outpatient therapy. The following day, she was seen again by her primary practitioner for re-evaluation and was given reassurance. The infant presents to the emergency department that same evening because her mother feels that her eye swelling has acutely worsened. In the emergency department, she has a temperature of 38.3°C and is admitted to the inpatient service to rule out sepsis.On admission, additional vital signs include a heart rate of 192 beats/min, respiratory rate of 47 breaths/min, and oxygen saturation of 100% in room air. On physical examination, the well-appearing infant has notable left upper and lower eyelid swelling as well as moderate left eye proptosis and mild conjunctivitis without discharge. The right eye appears normal. The infant has unrestricted range of motion of both eyes. The only other finding of note is a II/VI systolic ejection murmur heard best at the right sternal border. Family history is negative. Due to the patient's age, she receives a sepsis evaluation that includes cerebrospinal fluid (CSF) analysis and culture, urinalysis and urine culture, CBC, and blood culture. All of her initial studies are reassuring. Her CBC demonstrates a white blood cell count of 17.1×103/μL (17.1×109/L) with 37% neutrophils, 17% basophils, and 33% lymphocytes.During the physical examination, while the mother is undressing the girl, friction to the area of the skin lesion produces a bulla. The combination of this finding, the history of recurrent diarrhea, an unusual changing skin lesion, tachycardia, diaphoresis, and increased bowel sounds suggests the diagnosis of mastocytosis.Mastocytosis is the broad name for a spectrum of clinical disorders that are characterized by abnormal proliferation of mast cells in the skin or other organs. It may present during infancy, childhood, or adulthood, although most cases occur in the first 2 postnatal years, and more specifically in the first 6 months after birth. Mastocytosis has cutaneous and systemic forms, with the latter occurring in adults. The organ system most frequently involved is the skin, but the condition may also involve the lymphatic organs (spleen, liver, or lymph nodes), gastrointestinal system, bone marrow, or skeletal system. Cutaneous mastocytosis manifests as a solitary mastocytoma, urticaria pigmentosa, or diffuse cutaneous mastocytosis.Solitary mastocytosis is usually present at birth and consists of a round brown plaque or nodule up to a few centimeters in diameter. Solitary lesions may occur on the trunk, neck, or wrists, and the surface may resemble the pitted skin of an orange. Stroking or rubbing the affected skin results in a wheal-and-flare reaction due to the localized release of mast cell mediators, known as the Darier sign.Urticaria pigmentosa is the most common form of cutaneous mastocytosis and presents as small yellow-tan to reddish-brown macules or slightly raised papules. The upper and lower extremities are most commonly involved, although the face, scalp, thorax, and abdomen can also be affected.Diffuse cutaneous mastocytosis is of two types: urticarial and pachyerthrodermic, depending on the degree of infiltration of the skin by mast cells. In the urticarial form, the skin appears normal, but wheals develop easily, both spontaneously and after minor trauma. In the pacherythrodermic form, the skin is thickened and red-brown. Urticarial plaques and serous bullae are seen and associated with generalized itching.Pruritus is the most common presenting symptom in children who have mastocytosis, and it may be intermittent or unremitting. Other potential symptoms are flushing, gastrointestinal complaints (diarrhea, vomiting, colicky pain), and headaches. Prolonged bleeding sometimes can be seen in the skin or gastrointestinal tract. It is believed that bleeding in the skin may result from release of heparin contained in the skin's mast cells. Gastrointestinal hemorrhage appears to result from peptic ulcer formation due to high concentrations of circulating histamine. Blushing crises are also seen in mastocytosis. They occur suddenly, involve the face and upper trunk, last 10 to 30 minutes, and resolve without intervention. In extreme cases, anaphylaxis can be observed, which can result from either immunoglobulin E-mediated allergy or nonspecific activation of mast cells. Symptoms can include flushing, gastrointestinal symptoms, syncope, and vascular collapse. Urticaria and angioedema occur less frequently.Although rare, infants may present with a shocklike illness, consisting of bullous eruptions, gastrointestinal hemorrhage, or significant hypotension. In one case study (Murphy and associates), an infant died of massive hypotension due to mast cell degranulation. Therefore, any infant presenting with bullous lesions should have a thorough evaluation and be treated with supportive care as needed.The release of mast cell mediators in patients who have mastocytosis may be precipitated by a variety of stimuli. A careful history can be helpful in determining what may trigger an event in individual patients. Some known triggers include changes in temperature/weather (including heat, cold, humidity), emotional stress, exercise, spicy foods, alcohol, insect stings, infections (bacterial, viral, and ascarial), and certain medications, including morphine, codeine, nonsteroidal anti-inflammatory drugs, and vancomycin.Diagnosis is based on the clinical appearance of the cutaneous lesions. Plasma histamine concentrations generally are elevated. The diagnosis can be confirmed by documentation of significant mast cell hyperplasia on skin biopsy, but this invasive test should be reserved for patients in whom the diagnosis is not clear. Further evaluations, such as gastrointestinal radiography or endoscopy, can be performed if required. The cause of mastocytosis is unknown. Collectively, the various clinical forms are considered benign proliferative disorders of the reticuloendothelial system.The management of infant mastocytosis is generally symptomatic, ie, treatment of the pruritus or gastrointestinal symptoms. The drugs of choice are histamine-1 and -2 antihistamines in combination or individually. However, chronic antihistamine use can cause a concerning rebound effect when the treatment is stopped due to the large release of histamine. Therefore, short-term use is advised. Topical steroids have been shown to aid in the resolution of cutaneous symptoms. Oral sodium cromolyn can be administered for the gastrointestinal symptoms of diarrhea, abdominal pain, nausea, and vomiting. Cromoglycates have mast cell-stabilizing effects. This patient was diagnosed early and successfully treated with a short course of topical steroids and oral sodium cromolyn. Leukotriene inhibitors (including montelukast, zafirlukast, and zileuton) can be used as third-line agents, when symptoms are not fully controlled by antihistamines and cromoglycates. In older children, gradual sun exposure has been shown to be useful, although this is not recommended for infants.Infants who present only with bullae can be treated similarly to scald injury with blistering: local skin care and prevention of infection. Bullae generally heal without scarring but may leave an area of hyperpigmentation.Apart from medications, a major component of treatment is patient education. Patients/caregivers should avoid potential triggers that can cause mast cell degranulation. Care should be taken when the weather is very hot or humid. General measures can be employed, such as the use of lukewarm water baths rather than hot baths and avoidance of medications that are known to trigger reactions.Infants who present in a shocklike state should be stabilized promptly with intravenous fluids, glucocorticoids, antihistamines, or adrenaline. Furthermore, patients/caretakers should be trained to recognize and treat anaphylaxis with epinephrine in case of anaphylactic shock.Even though it is comparatively rare in the neonatal period, mastocytosis should be considered in infants who present with a solitary or diffuse dermatologic lesions that, upon stroking, develop a wheal-and-flare reaction. Particularly concerning is an infant presenting in a shocklike state, who requires prompt and aggressive supportive care. Such patients should be monitored in the intensive care setting and treated with antihistamines, fluid support, and epinephrine, when necessary.Other systems, including the reticuloendothelial system and the gastrointestinal tract, may be involved, necessitating a thorough history and physical examination. Treatment for nonemergent cases involves antihistamines, topical steroids, and oral sodium cromolyn (for gastrointestinal symptoms) as well as avoidance of triggers. Early diagnosis and treatment is essential in limiting long-term morbidity.Laboratory tests reveal the presence of a minor rhesus antigen, Cw, on the neonatal red blood cells. After transfer to the neonatal intensive care unit, the infant is treated with two doses of immune globulin intravenous (IGIV) and two transfusions of packed red blood cells (RBCs). Before receiving treatment, the hematocrit reaches a nadir of 23% (0.23) and the TsB peaks at 17 mg/dL (290.8 μmol/L). The infant is treated with quadruple phototherapy for a total of 6 days. On the seventh day, she is discharged from the hospital with a TsB of 11.8 mg/dL (201.8 μmol/L). Two days later, she is readmitted to the hospital with a TsB of 15.8 mg/dL (270.2 μmol/L). Triple phototherapy is reinitiated. Following an additional 28 hours of inpatient phototherapy, the infant is discharged with a fiberoptic blanket that is used until 16 days after birth. At 17 days age, the TsB is 10.4 mg/dL (177.9 μmol/L) and stable.Hemolytic disease was first described in the early 1600s. Much progress has been made since then in terms of possible causes, diagnostic methods, and even treatment. The underlying pathogenesis involves passage of maternal antibodies across the placenta into the fetal bloodstream. The antibodies target and attach to antigens on the fetal red blood cells, ultimately leading to hemolysis (mostly extravascular).Some of the antibodies are innate, such as in ABO incompatibility, but many are formed as a result of maternal exposure to fetal antigens, either during delivery or at some point during pregnancy. Studies have shown that more than 60 RBC antigens are associated with hemolytic disease of the newborn (HDN). Much of the variation is due to proteinaceous antigens that are embedded in the cell walls of RBCs.Clinically, HDN can vary from very mild to severe disease, even resulting in death. Clinicians should become concerned about hemolysis when a newborn appears jaundiced at less than 24 hours after birth and especially if the TsB reaches 12 mg/dL (205.2 μmol/L) or higher. Clinical features of HDN include: anemia, jaundice, and hepatosplenomegaly. Fetal blood typing and a DAT are required to make a definitive diagnosis. Treatment options include phototherapy, IGIV, and exchange transfusion. Phototherapy is the least invasive option and is often viewed as a first line of treatment, with IGIV being an effective adjunct to therapy. In addition, studies have shown that IGIV is an effective measure for decreasing the need for exchange transfusion. The exact mechanism of IGIV is unknown, but the most widely accepted hypothesis is that it interferes with the Fc receptors, especially within the reticuloendothelial system in the case of RBC hemolysis.Exchange transfusion is a more invasive procedure in which a patient's blood is removed from his or her circulation and replaced with new blood. In the case of HDN, the goals are to remove the bilirubin and maternal antibodies from the newborn's bloodstream, while simultaneously correcting the anemia by replacing the old RBCs with antigen-negative RBCs.Four cases of HDN due to antibodies targeting the Cw antigen have been reported in the United States, most recently in 2007. Ultimately, it is important to be aware of the uncommon causes because the clinical spectrum is widely variable. Some investigators have even raised the concern that minor blood group antigens may result in increased morbidity with the advent and widespread use of Rho(D) immune globulin. This is based on the fact that the use of Rho(D) immune globulin has significantly decreased the incidence of hemolytic disease due to the Rh D antigen.Today, many people are aware of the dangers associated with ABO incompatibility and hemolysis due to antibodies binding to the Rh D antigen, but minor blood group antigens also are important. It is imperative that clinicians remain vigilant in testing for antigens that were once believed to be a cause of only minor disease.Computed tomography (CT) scan of the left orbit (Fig. 2) showed moderate proptosis of the left eye, left orbital cellulitis, edema in the left medial orbit without abscess, and left ethmoid sinusitis. Fluorescein dye examination of the patient's left eye on admission was negative for keratitis and showed only minor abrasions due to mechanical trauma. Dilated funduscopic examination performed by pediatric ophthalmology also yielded normal results.Nasopharyngeal swab of the left naris grew methicillin-resistant Staphylococcus aureus (MRSA) sensitive to clindamycin, vancomycin, gentamicin, trimethoprim-sulfamethoxazole, rifampin, and tetracycline. Within 48 hours, the blood culture also grew MRSA with the same sensitivity profile. The mother's nares were swabbed and were positive for MRSA, but sensitivities were not determined on this sample. To evaluate the patient's cardiac murmur further in the setting of a staphylococcal bacteremia, two-dimensional echocardiography was performed and yielded negative results.The patient initially received ampicillin and gentamicin, with clindamycin added due to clinical concern for MRSA. Initially, no improvement of her proptosis was apparent, and magnetic resonance imaging of the left orbit on hospital day 5 showed progression of the orbital cellulitis, with an 8×26×18×9-mm phlegmon versus in the left orbit with Because the patient had been from 48 hours after and was doing well with decreased the orbit and normal examination medical management was with intravenous for 6 more days. was on hospital day Because the proptosis had she was on oral clindamycin and discharged from the hospital to complete 10 additional days for a total of days of blood culture 48 hours after admission negative. and urine were negative for reaction testing also showed negative is an to the orbital that is most commonly due to from an in an The ethmoid is the most common symptoms include and of the It may progress to proptosis and and with of the symptoms may also be not is of the may to such as or in pediatric orbital are and staphylococcal However, cases an of MRSA in is rare in with only about 10 and the cases of neonatal orbital reported in the in to two of cases and that the condition most often is associated with an staphylococcal This has been shown to be in case They that this finding is due to the of the ethmoid cells are the first to develop and are present at birth. The the orbit from the ethmoid and may as a of the two healthy term infants are known to be with normal from and in the first few days after birth, with aureus being a common immune is in at for more invasive In orbital may rapidly progress to and management of orbital includes of the primary of the and within the orbit as well as of the and of a pediatric and pediatric is scan of the orbit of the of and the presence or of especially who have orbital should be evaluated for sepsis because of the high rate of progression to or should be if is treatment with intravenous the with on MRSA, should be initiated, but many patients if symptoms should be considered when a presents with of the eyelid that to should be treated in the hospital with scan of the orbit to the of the of or for culture, evaluation for frequent and of intravenous should include the most including staphylococcal to a treatment with intravenous may be if the patient is However, many patients