JOURNAL CLUB

Commentaries By Michael G. Burke, MD

Are anaphylactic reactions often biphasic?

Because recurrences of anaphylactic symptoms after an initial remission can be severe, many hospitals monitor children with an episode of anaphylaxis for eight to 24 hours. Investigators conducted a retrospective analysis of more than 100 anaphylactic episodes in children to determine just how common biphasic reactions are. The children ranged in age from 6 months to 21 years, and 69 of them had a positive atopic history for asthma, eczema, or allergic rhinitis. Of 92 cases with an identified trigger, food was the most common culprit, especially tree nuts, peanuts, and seafood. The most common serious symptoms were respiratory, but cardiovascular, dermatologic, gastrointestinal, and neurologic symptoms also were seen.

Six (6%) of 105 children whose initial anaphylactic symptoms resolved had additional reactions later. In three of these six the biphasic reactions were serious. In one, in fact, the second set of reactions were more severe than the first. The interval between resolution to onset of biphasic reaction ranged from 1.3 hours to 28.4 hours. All of the patients with biphasic reactions had been treated with subcutaneous epinephrine in the initial phase of anaphylaxis, and five of the six had received steroids. In all six patients, the biphasic reaction affected the same organ systems as did the initial anaphylactic reaction. In patients with biphasic reactions the time between onset of symptoms and the initial dose of epinephrine was significantly longer than for patients who did not have biphasic reactions. No other clinical risk factors identified patients who would have biphasic reactions (Lee JM et al: Pediatrics 2000;106:762).

Commentary: The 6% rate of relapse reported here is less than the 23% observed in a group of 13 patients with severe anaphylaxis reported by Sampson et al (N Engl J Med 1992;327:380). Nonetheless, 6%, more than one in 20, is enough for me to want to watch these children for a day before discharge. Call me chicken.

Chitterlings dangerous for infants

A retrospective review of the medical and microbiologic records of 1,120 children who presented to a large hospital with bacterial enteritis during a seven-year period revealed that Yersinia enterocolitica is an important cause of this illness during the winter holidays. Children exposed to chitterlings (raw pork intestines) or to adults who have prepared chitterlings are at particular risk.

Y enterocolitica accounted for 142 (12.6%) of positive stool cultures. Children with Yersinia enteritis ranged in age from 18 days to 12 years, though most (85%) were younger than 1 year. In 25 of 30 patients whose families were questioned, the child had been exposed to chitterlings prepared at home before the child became ill. Most of the patients (74%) had fever, and one half had bloody stools. Common laboratory features were leukocytosis, increased band forms, monocytosis, and thrombocytosis. Infants younger than 3 months with Yersinia enteritis were at greater risk for bacteremia than were older children. Sixty patients (42%) required hospitalization, mostly because of dehydration or suspected sepsis, and 82 (58%) were managed as outpatients. All bacteremic patients responded to cefotaxime treatment.

Yersinia isolates recovered from the patients were susceptible to trimethoprim-sulfamethoxazole, tobramycin, and gentamicin. More of the isolates were susceptible to cefotaxime (99%) than to ceftazidime (89%). In strains resistant to ceftazidime, the level of resistance generally was high.

Follow up of 40 ambulatory patients showed no difference in clinical improvement between those treated with oral trimethoprim-sulfamethoxazole and those who were not treated (Abdel-Haq NM et al: Pediatr Infect Dis J 2000;19:954).

Commentary: Most (84%) of these cases presented in November, December, or January, perhaps a reflection of holiday preparation of chitterlings. And 17% of those with Y enterocolitica in their stools were also positive for rotavirus antigen. Keep this in mind as you approach your rotavirus season this year.

Rickettsial disease? Consider doxycycline

Investigators hypothesized that because of the potential of tetracyclines to stain teeth, cause phototoxic eruptions, and produce other adverse effects, general pediatricians are not prescribing this class of drugs, even when they strongly suspect rickettsial infection. Yet most experts now consider doxycycline the drug of choice for children in whom rickettsial infection, such as Rocky Mountain spotted fever (RMSF), ehrlichiosis, or murine typhus, is presumed or proved. To test their hypothesis, investigators reviewed the medical records of 35 children 17 years or younger who received a coded diagnosis of rickettsiosis or a specific rickettsial disease or for whom rickettsial serology was ordered. Of this group, 30 children (86%) presented with fever, 21 (60%) with rash, and 14 (40%) with headache, typical presenting symptoms for rickettsial diseases. Some children also had laboratory findings consistent with rickettsial diseases.

Only one patient (3%) received a tetracycline class antibiotic as initial empiric therapy. Most often, the child was not prescribed any antibiotic when admitted. When a specific antirickettsial antibiotic was used (in 19 or 54% of patients), it was generally at the recommendation of an infectious disease specialist. Only 11 patients (31%) received doxycycline, the antirickettsial antibiotic with the safest side effect profile and the least potential for causing tooth staining (Purvis JJ et al: Pediatric Infect Dis J 2000;19:871).

Commentary: And on those warm summer days when you are not worrying about Yersinia or rotavirus, keep RMSF and other tick-borne diseases well in mind. In a report of four cases of RMSF, the MMWR makes the same point as these authors: Pediatricians are often hesitant to start doxycycline, even when they strongly suspect rickettsial disease (MMWR 2000; 49(39):885). This is frequently a clinical diagnosis, one that can't wait for laboratory results. And the classic triad of fever, rash, and history of tick exposure is present in only 3% to 18% of cases. So, during the summertime, keep your guard up and your threshold for initiation of doxycycline low.

Intravenous Mg: A magic bullet for asthma?

Intravenous magnesium sulfate produces a remarkable improvement in short-term pulmonary function in children with moderate to severe asthma exacerbations, a new study shows. Investigators followed 30 children from 6 to 17.9 years old who presented to an emergency department with an acute asthma exacerbation. These children had a suboptimal response to ß-agonist therapy. Half the patients were given a magnesium sulfate infusion (IVMg) of 40/mg/kg to a maximum dose of 2 g and half received a saline solution. Pulmonary function tests showed significant improvement in patients who received IVMg compared with those who received the placebo infusion. At the conclusion of the infusion, which took 20 minutes, improvements from baseline in the magnesium group in predicted peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were far greater than in the placebo group. The relative improvement was even more marked at 110 minutes, with peak expiratory flow rate improved 25.8% in the magnesium group compared with 1.9% in the placebo group, forced expiratory volume in 1 second 24.1% vs. 2.3%, and forced vital capacity 27.3% vs. 2.6%. At the end of the assessment period, all 14 of the placebo-treated patients needed to be admitted to the hospital, whereas eight (50%) of 16 patients who received IVMg were discharged to their homes. Improvement continued in those who were discharged, and none of these patients needed to return to the emergency department or be hospitalized. Clinical asthma scores also were better in the IVMg group than in the placebo group, but these differences were not apparent until 95 minutes after infusion (Ciarallo L et al: Arch Pediatr Adolesc Med 2000; 154:979).

Commentary: Use of magnesium for asthma is not new. The new message here is to give Mg earlier and in higher doses than previously described. I bet that in the future we'll see still higher doses and an increase in the maximum recommended dose.

Using longer needle reduces vaccine reactions

Use of 25 mm needles instead of 16 mm needles for routine immunizations significantly reduces rates of local reactions to routine infant immunization, according to a study from the United Kingdom. The 110 4-month-old infants in the study were divided into two groups for administration of the third dose of diphtheria, pertussis, and tetanus (DTaP) and Haemophilus influenzae type b (Hib) vaccines. One group received the vaccine via a 25 gauge, 16 mm needle and the other with a 23 gauge, 25 mm needle. Parents recorded redness, swelling, and tenderness in a diary for three days after immunization. Six hours after vaccination, 34 infants immunized with the shorter needle had redness at the injection site compared with 21 infants vaccinated with the longer needle (60% vs. 40%). By the third day, the gap had widened even further with 16 (28%) of infants in the short needle group having redness compared with two (4%) in the long needle group. Similarly, 33 (58%) of infants initially had swelling after injection with the shorter needle compared with 12 (23%) vaccinated with the longer needle, and this difference was maintained for all three days. Although use of the longer needle also resulted in less tenderness than use of the shorter needle, these differences were not significant (Diggle L et al: BMJ 2000;321:931).

Commentary: Here's the surprise: The longer, bigger-bore needle produced less swelling and redness than the smaller needle. For every five patients vaccinated with the longer needle, one local reaction would be avoided. The authors speculate that the longer needle may ensure that the shot is given intramuscularly instead of subcutaneously. They wonder if converting to this lower-risk needle would improve parent compliance with prescribed vaccine immunization schedules. Sounds like it is worth a try.

Turner syndrome diagnosis often delayed

A study of 81 girls with Turner syndrome (TS) shows that this condition often is not diagnosed until late childhood or adolescence despite growth failure and the presence of numerous typical historical and physical characteristics of TS. The mean age at diagnosis for the 81 patients was 4.2 years and ranged from prenatal life to 16.8 years. Lymphedema or webbed neck was present in all patients diagnosed at birth. Six of 38 patients (16%) who had a history of lymphedema at birth did not get a diagnosis in infancy, however. Of patients who received a diagnosis in childhood or adolescence, 25 of 39 (64%) had lymphedema at birth or two or more of the dysmorphic features, such as webbed neck, nail dysplasia, high palate, and short fourth metacarpal, that might have led to the diagnosis of TS at birth. These patients did not receive a diagnosis until an average of 9.1 years later.

After infancy, short stature was the feature that most often led to an evaluation by karyotype. The interval between decline in height below the fifth percentile and diagnosis was long, however, a mean of 5.2 years. Patients exhibited multiple clinical features as well as short stature that might have served as diagnostic clues for TS. They had medical problems such as delayed puberty, nonverbal learning disabilities, feeding difficulties during infancy, coarctation of the aorta, or strabismus, in addition to the common dysmorphic features listed above. Investigators estimated that overall delay in diagnosis of TS for patients whose condition was recognized in childhood or adolescence was 7.7 years (Sävendahl L et al: J Pediatr 2000;137:455).

Commentary: To avoid delay in diagnosis of Turner syndrome, the authors offer these guidelines for screening. Consider a karyotype in all girls with unexplained short stature (< fifth percentile), webbed neck, peripheral lymphedema, coarctation or the aorta, or delayed puberty (absence of Tanner 2 breast development at 12.5 years). Also consider screening in girls with two or more of these features: nail dysplasia, high arched palate, short fourth metacarpal, and strabismus.

A better way to predict bacteremia?

Investigators developed a new model for ascertaining whether a febrile patient has bacteremia. They performed a retrospective review on 633 patients from 3 to 36 months of age seen in a children's hospital emergency department during a one-year period for whom a complete blood count (CBC) and blood culture were ordered. They then used analytical techniques to identify factors associated with bacteremia and validated the resulting model on a second dataset drawn from febrile patients of the same age collected from a second children's hospital. Predictors of bacteremia identified by logistic regression included absolute neutrophil count (ANC), white blood cell count (WBC), polymorphonuclear cell count, temperature, and gender, with female gender significantly associated with bacteremia. The analysis suggests that having a high ANC (>9.46) or WBC value (>14.3) may be the strongest indication that a child will develop bacteremia (Isaacman DJ et al: Pediatrics 2000;106:977).

Commentary: Will these studies on prediction of bacteremia all need to be redone in the era of universal vaccination of infants for pneumococcus? Probably. The prevalence of bacteremia should fall, making the chances of a false-positive screen more likely. Stay tuned.

Zanamivir prevents family spread of influenza

Prophylaxis with zanamivir is an effective option for preventing the transmission of influenza within households, according to a new study. Investigators divided 337 families that had one member with an influenza type illness into two treatment groups. Family members with index cases of influenza received either inhaled zanamivir (10 mg) or placebo twice a day for five days. The other healthy family members received the same study drug as the ill member in their household, either zanamivir (10 mg) or placebo once daily for 10 days.

Among families in which the index illness was laboratory-confirmed influenza, the proportion in which influenza developed in contacts was 29% in the placebo group and 8% in the zanamivir group. Among families in which the index illness proved not to be influenza, the proportions were 8% and 1%, respectively. The rate of zanamivir protection against influenza in healthy household contacts was 79% overall, 72% in the families with confirmed influenza, and 87% in the group with influenza-negative index cases. Zanamivir prophylaxis was effective against both influenza A and influenza B, did not appear to be related to development of zanamivir-resistant influenza variants, and was well tolerated. In addition, among the subjects with index cases of laboratory-confirmed influenza, the median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (Hayden FG et al: N Engl J Med 2000; 343:1282).

Commentary: This may be big news for families in flu season and also for residents of long-term care facilities and other groups of high-risk individuals.

Also of note

Consider sumatriptan for teen migraine. A new study of sumatriptan nasal spray in the treatment of acute migraine in adolescents offers considerable evidence of the efficacy, tolerability, and safety of the agent in this age group. The 510 teen migraine patients who completed the study ranged in age from 12 to 17 years. They were treated with sumatriptan nasal spray in a 5-, 10-, or 20-mg dose or with placebo. Patients treated with all three dosages of sumatriptan were more likely than controls to report relief of symptoms. Patients in the 10-mg and 20-mg treatment groups reported more relief as early as one hour after taking the medication. Patients from 12 to 14 years of age reported higher efficacy rates at lower doses of sumatriptan, while older patients from 15 to 17 years of age reported the highest efficacy at the 20-mg dose. Phonophobia and photophobia, which were common at baseline, were significantly reduced in the 20-mg sumatriptan nasal spray treatment group by two hours after treatment. Disturbance of taste was the most frequent adverse event reported with treatment. Incidence of other adverse events was similar in both treatment and placebo control groups (Winner P et al: Pediatrics 2000;106:989).

B henselae infection may mimic mononucleosis. Italian investigators reported on six children with clinical features of infectious mononucleosis in whom appropriate serology showed infection with Bartonella henselae. The six patients, all 5 years old or younger, presented with persistent fever, pharyngitis, tonsillitis with or without exudate, nasal obstruction, periorbital edema, painless bilateral cervical and submandibular lymphadenitis, and splenomegaly. All had negative serology for Epstein-Barr virus, cytomegalovirus, adenovirus, and Toxoplasma gondii but were positive for both immunoglobulin M and immunoglobulin G to B henselae. Other laboratory features included elevated white blood cells with a left shift, elevated erythrocyte sedimentation rates and C-reactive proteins, and hypergammaglobulinemia. All six children had a history of contact with a kitten (Massei F et al: Arch Dis Child 2000;83:443).

DR. BURKE, Section Editor for Journal Club, is Chairman of the Department of Pediatrics at Saint Agnes Hospital, Baltimore. He is a Contributing Editor for Contemporary Pediatrics.

CLINICAL TIP

Cold compresses: The power of example

When a young child refuses to allow a cold pack to be placed on an injury (usually the forehead), have the family make up three or four small cold packs for themselves or the child's favorite doll or teddy bear. After seeing the compresses in use, the curious child will occasionally apply the cold pack to himself to imitate his parents or an older sibling. Even if he won't do it himself, the child will often let the caregiver apply the cold pack to his injury once he has watched how it works on someone else.

Carl S. Ingber, MD
Pebble Beach, CA

Approach this problem from behind

When you think a toddler is going to cry as soon as you approach with the stethoscope, or even as soon as the mother moves or places the child on the exam table, try this: First, explain to the mother that you are going to step out of the room for 10 to 15 seconds. Tell her she should wait for you to leave and then stand up and face the door, holding the child in her arms with his head on her shoulder, looking away from the door.

On quietly re-entering the room, you can auscultate the toddler's back through a thin cotton shirt with a warmed stethoscope without frightening him. If another person, such as a significant other or older sibling, is also in the room, he or she can distract the toddler's attention by standing behind the mother and showing the child a toy or a sticker.

The essence of my approach is that the infant doesn't have face-to-face interaction with the physician or nurse during the initial auscultation. Nurses in the emergency department are always amazed that I am able to perform auscultation with little or no complaint from the toddler, when before they heard nothing but crying.

Carl S. Ingber, MD
Pebble Beach, CA

Inhalers for the very young: It's all in the timing

One of the most popular spacing devices for metered-dose inhalers (MDIs) is the Inspirease. Although this device works well with children over 5 years of age, younger patients commonly blow into the bag instead of inhaling

The following technique works nicely with 3- to 5-year-olds: Place the mouthpiece in the child's mouth with the bag collapsed. Next, ask the child to breathe in and out. The child will blow out first, expanding the bag, and then breathe in again. Trigger the MDI with the second breath (when the bag is expanded) and encourage the child to continue breathing in and out. After the patient has completed four cycles, trigger the MDI for the second dose. This technique enables a young child to use the device properly about 75% of the time.

Howard Bennett, MD
Bethesda, MD

A smooth move for closing cuts

When closing a laceration with topical skin adhesive or tissue glue, I use two tongue depressors to approximate the edges of the wound. I have an assistant place the long edge of each tongue blade on either side of the long axis of the cut about 1 cm from the edge of the laceration. The assistant then pushes the two blades toward each other Once we are satisfied with the wound approximation, I apply the glue. This technique produces excellent approximation while maintaining good visibility of the wound. Best of all, because both hands are free, it allows you to apply the glue evenly so that you don't glue yourself to the patient. Two tongue blades are significantly less expensive than forceps or other instruments that could be used to assist in closing a laceration, a consideration in these days of controlled costs.

Randy J. Goldstein, MD
El Paso, TX

Do you have a Clinical Tip to share with colleagues? Let us know; we'll pay $50 for each item accepted for publication. Tips sent by mail should be addressed to Molly Frederick, Clinical Tips Editor, Contemporary Pediatrics, 5 Paragon Drive, Montvale, NJ 07645-1742. If you submit by e-mail (Molly.Frederick@medec.com), please include your mailing address.

 

Michael Burke. Journal Club. Contemporary Pediatrics 2001;1:129.