A 7-month-old girl presents to her pediatrician’s office with a 1-week history of fevers and upper respiratory symptoms.

The infant had no past medical history and her immunizations were up-to-date. She had some decreased appetite and occasional fussiness, but was otherwise acting appropriately for her age. She had normal urine output. Because of the 1-week history of fevers and rhinorrhea, the pediatrician obtained laboratory studies revealing normocytic anemia and thrombocytosis. The infant was then referred to the emergency department (ED) for further evaluation.

On initial presentation, the patient was febrile to 102.56°F; heart rate was 185 beats per minute; respiratory rate of 36 breaths per minute; blood pressure of 97/49 mm Hg; and oxygen saturation of 99% on room air. Physical exam revealed an active 7-month-old girl in no acute distress but found to be pale and nonjaundiced. She had a regular cardiac rate and rhythm without a murmur. Lungs were clear to auscultation bilaterally without increased work of breathing, wheezing, or crackles. Abdomen was soft, nontender, nondistended with active bowel sounds, and with no hepatosplenomegaly or palpable masses. Her remaining physical exam was normal and appropriate for age.

Initial laboratory results demonstrated a white blood cell count (WBC) of 9.1 K/mcL; absolute neutrophil count (ANC) of 0.3 K/mcL; hemoglobin of 7.8 gm/dL with mean corpuscular volume (MCV) of 79.9 fL; hematocrit, 24.3%; and platelets, 633 K/mcL. Comprehensive metabolic panel was normal, specifically aspartate aminotransferase (AST), 23 unit/L; alanine aminotransferase (ALT), 17 unit/L; alkaline phosphatase, 142 unit/L; and total bilirubin, 0.2 mg/dL.

Inflammatory markers were elevated with C-reactive protein (CRP) of 26.8 mg/dL and erythrocyte sedimentation rate (ESR) greater than 120 mm/h. Iron studies were: iron, 9 mcg/dL; total iron binding capacity (TIBC), 114 mcg/dL; iron saturation, 8%; and ferritin, 434 ng/mL, not exclusively consistent with iron-deficiency anemia. A blood culture and nasopharyngeal respiratory pathogen panel was obtained.

The patient was admitted to the general pediatric unit for febrile neutropenia and was started on cefepime for empiric bacterial antibiotic coverage. Due to potential malignancy, the patient had an abdominal ultrasound that showed a 6.4-cm hepatic mass, confirmed with an abdominal computed tomography (CT) scan (Figure 1).

The patient’s main abnormal vital sign/physical exam finding was fever. She had several initial laboratory abnormalities including severe neutropenia, normocytic anemia, thrombocytosis, and elevated inflammatory markers. Also, she was found to have a nonspecific hepatic mass on imaging, although nonpalpable on physical exam.

This patient’s presentation was concerning for sepsis and malignancy, and thorough evaluation was needed. Such patients require consultation with pediatric subspecialists at the time of presentation, which may require transferring the patient to a tertiary care center. This infant was admitted to a tertiary children’s hospital where subspecialty consultation was readily available. In a patient with fever and neutropenia, prompt initiation of antibiotic therapy for potential sepsis is important, and this empiric coverage should continue until an infectious bacterial process has been ruled out.

For any child who presents with a liver mass, benign or malignant tumors are highly suspected, with malignant tumors being most concerning and requiring prompt evaluation. Hemangioma and hamartoma are the most common liver masses in infants aged younger than 1 year. These lesions often are visualized on abdominal ultrasound, CT, or magnetic resonance imaging (MRI). Hepatoblastoma and hepatocellular carcinoma also are on the differential, which requires a confirmatory biopsy when the patient is clinically stable. Additional imaging may be warranted if there is concern for metastatic disease.

Given the patient's fever, an infectious etiology was suspected, such as abscesses or viral hepatitis, and required further laboratory studies. Although uncommon, 

 should be considered because of its propensity to form liver abscesses, especially with a history of international travel.

Febrile neutropenia can be caused by viral suppression of bone marrow function. However, given the additional abnormal findings in this patient (ie, elevated inflammatory markers and hepatic mass), timely involvement of pediatric subspecialists and further workup were needed. The Hematology/Oncology team was consulted for febrile neutropenia, anemia, and thrombocytosis with concerns for a possible oncologic etiology, and the Infectious Disease team for possible infectious process as the cause of her signs and symptoms.

The patient continued to be febrile while on cefepime. Her blood culture was negative. She was found to have enterovirus/rhinovirus on her respiratory viral polymerase chain reaction (PCR) panel, likely the source of her fever. Her remaining infectious disease workup was negative, specifically for hepatitis, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and 

. Sepsis was ruled out given that her blood culture was negative. The child remained well appearing throughout her hospitalization and had a negative infectious disease workup.

She underwent a bone marrow biopsy that was negative for malignancy. A fine needle biopsy of the hepatic lesion was performed initially, but this was not diagnostic. Subsequently, she had an open liver biopsy, which demonstrated a right-lobe hepatic mass with pathology showing abundant mixed lymphoplasmacytic infiltrate and positive immunoglobulin (Ig) G4 plasma cells, consistent with inflammatory pseudotumor (Figure 2).

Additional laboratory studies including normal alpha-fetoprotein and beta-hCG levels were negative, but showed positive granulocyte antibodies. Genetic congenital neutropenia panel was also negative. All immunoglobulin levels (IgG, IgM, and IgA) were elevated.

Inflammatory pseudotumors (IPT) are rare, benign, solitary, well-demarcated lesions caused by proliferation of inflammatory cells.

 Other terminology used to describe IPT includes inflammatory myofibroblastic tumor, plasma cell granuloma, fibrous histiocytoma, fibroxanthoma, and xanthogranuloma. This type of benign lesion is most commonly found in the lung, although extrapulmonary sites have been identified, including the head and neck regions, orbit, major salivary glands, submandibular glands, lymph nodes, breast, kidney, pancreas, gastrointestinal (GI) tract, liver, spleen, retroperitoneum, genitourinary tract, and soft tissue. As of 2011, fewer than 300 cases of hepatic inflammatory pseudotumor have been identified and reported.

 From 1971 to 2008, only 35 pediatric cases were reported with an additional 9 pediatric cases from 2009-2014. Increased IPT identification can be attributed to advances in medical imaging.

Because of a variety of constitutional symptoms (fever, malaise, weight loss, and fatigue) and difficulty in accurately diagnosing IPT, patients often are misdiagnosed initially with malignancy. The majority of documented IPTs are asymptomatic, incidental findings. Although extremely rare, severe lesions causing mass effect have been reported as well.

Initial laboratory studies usually are significant for elevated WBC count, elevated acute phase reactants such as ESR and CRP, and abnormal liver function tests (LFTs). Although uncommon, IPT can cause cytopenias affecting WBC, specifically, neutrophils (ANC), hemoglobin, and/or platelets. Ultrasound, CT, MRI, and positron emission tomography (PET) imaging can demonstrate variable clinical images based on location and density of the affected lesion. If diagnosis remains unknown, patients often undergo fine-needle aspiration (FNA) or open biopsy/resection to determine a diagnosis.

Inflammatory pseudotumor typically develops secondary to an aberrant inflammatory response from a cellular insult. Histologically, when inflammatory cells are activated, various cytokines are produced and released. These cytokines activate neutrophils, eosinophils, lymphocytes, plasma cells, histiocytes, multinucleated giant cells, myofibroblasts, and spindle-shaped cells, leading to cellular damage and IPT formation.

Although the etiology of IPT remains unknown, several possibilities have been proposed, ranging from postinfectious to autoimmune to neoplastic causes. Inflammatory pseudotumors have been identified after postradiation therapy for malignant neoplasms.

 Several IPT lesions show anaplastic lymphoma kinase positivity at the tyrosine kinase locus, supporting a theory that plasma cell granulomas are low-grade mesenchymal neoplasms with a secondary inflammatory component.

Previously reported cases have not demonstrated a correlation between inflammatory pseudotumor and severe neutropenia, leading to this perplexing case. Generally, patients diagnosed with IPT do not require inpatient hospitalization and can be monitored on an outpatient basis. This patient’s diagnosis remained unknown for multiple days and was complicated by continued fevers and severe neutropenia with initial concerns for malignancy, causing her prolonged hospitalization. The persistent neutropenia was likely secondary to a combination of inflammatory pseudotumor of the liver, viral illness with enterovirus/rhinovirus, and autoimmune neutropenia. Although, the etiology and long-term implications of this patient’s IPT and neutropenia remain unknown, the concomitant presentation suggests a potential association between the two. 

Inflammatory pseudotumor can be a manifestation of IgG4-related disease, an immune-mediated condition characterized by lymphoplasmacytic infiltration with a predominance of immunoglobulin G4-positive plasma cells, frequent elevation of serum IgG4, and a dramatic response to glucocorticoids, if administered.

 Initially, this patient had elevated serum IgG4 levels, which normalized over time, and liver pathology was positive for IgG4 plasma cells. Given these laboratory and pathology findings, the patient’s IPT appears to be consistent with the lymphoplasmacytic subtype. Although glucocorticoids are found to be effective, this patient did not receive steroids because of her improved fever curve and continued hemodynamic stability throughout her hospitalization.

In most instances of postinfectious neutropenia, particularly with viral infections, neutropenia is transient and rarely results in superimposed bacterial infections. Other viral infections known to cause mild to moderate neutropenia also include influenza A and B, respiratory syncytial virus (RSV), and parvovirus.

 Measles, rubella, and varicella more commonly cause leukopenia with mild neutropenia and lymphopenia. Viruses leading to greater immune suppression include EBV, CMV, human herpesvirus-6 (HHV-6), hepatitis, and human immunodeficiency virus (HIV), which can cause more superimposed bacterial infections.

Previous reports have demonstrated improvements in neutropenia in 3 to 8 days. However, the patient in this case remained persistently neutropenic throughout her hospital course.

 Prolonged fevers and neutropenia always raise concern for possible sepsis. Luckily, she was diagnosed with enterovirus/rhinovirus without secondary infectious etiologies.

Autoimmune neutropenia (AIN), caused by granulocyte-specific antibodies, is commonly diagnosed between ages 7 to 9 months.

 Patients often are incidentally diagnosed when laboratory studies are obtained for other reasons with an initial ANC ranging from 0.5 to 1.0 K/mcL.

 Diagnosing AIN can be challenging because of difficulties in detecting autoantibodies, and AIN is most commonly diagnosed with the indirect granulocyte immunofluorescence test (indirect-GIFT) or the granulocyte agglutination test (GAT).

 This patient underwent testing and was found to have positive granulocyte antibodies with chronic neutropenia, thereby diagnosing her with a component of autoimmune neutropenia. Treatment typically includes close monitoring with spontaneous remission and disappearance of autoantibodies.

Patients with recurrent or severe infections or those undergoing surgical procedures often receive filgrastim-G-CSF.

 Escalating therapy for refractory cases include intravenous immunoglobulin (IVIG), corticosteroids, or monoclonal antibodies.

 Although the patient in this case did not have a severe viral infection, she remained persistently neutropenic without improvement, leading to the decision to start treatment with G-CSF.

Among the few reported cases of IPT, even fewer have been associated with neutropenia.

 Cojean and colleagues describe a patient with severe congenital neutropenia concurrently diagnosed with IPT through positron emission tomography (PET) imaging, which occurred after an unsuccessful response to G-CSF in anticipation of bone marrow transplantation (BMT).

 As IPT has not been consistently associated with neutropenia, a plausible connection could be neutropenic patients becoming more susceptible to developing IPT after recovery from a cellular insult secondary to an infection. Although rare, it is important to consider inflammatory pseudotumor when there are concerns for a mass with or without significant neutropenia, as this lesion does not always require inpatient hospitalization, medications, or surgical intervention.

Treatment options are usually conservative but can require surgical resection if no clinical improvement is observed. First-line treatment includes outpatient monitoring with serial imaging, frequent ultrasounds, and repeat laboratory studies. If IPT continues to persist, patients often undergo full resection. After surgical intervention, most cases of IPT do not recur. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics also have been utilized with varying responses. If an IgG4-related disease is suspected, glucocorticoids can help with tumor regression.

During her 19-day hospitalization, the patient’s neutropenia continued and the decision was made to start G-CSF. She was discharged once she was no longer febrile with improvement in her ANC, anemia, thrombocytosis, and inflammatory markers. Because of the location and size of her hepatic lesion, she was not a candidate for a complete resection at the time of her open biopsy. She continued conservative treatment with serial imaging and repeat laboratory studies.

Initially, she was receiving serial abdominal ultrasounds monthly, then extended to bimonthly with an abdominal MRI scan demonstrating complete regression of the hepatic inflammatory pseudotumor 9 months after the initial diagnosis (Figure 2). Luckily, this patient had spontaneous regression and did not require surgical resection of her IPT. She remained on G-CSF for 4 months as outpatient therapy with improvement in chronic neutropenia. Repeat Ig levels also normalized. Overall, her clinical course improved significantly with regression of her IPT and normalization of abnormal laboratory studies.

: The authors wish to thank Michael Pins, MD, and Christine Salibay, DO, for their contribution to this case report.

1. Al-Hussaini H, Azouz H, Abu-Zaid A. Hepatic inflammatory pseudotumor presenting in an 8-year-old boy: a case report and review of literature. 

2. Nagarajan S, Jayabose S, McBride W, et al. Inflammatory myofibroblastic tumor of the liver in children. 

3. Weinberger SE. Inflammatory myofibroblastic tumor (plasma cell granuloma) of the lung. UpToDate.com. Avalilable at: 

https://www.uptodate.com/contents/inflammatory-myofibroblastic-tumor-plasma-cell-granuloma-of-the-lung?source=search_result&search=inflammatory%20pseudotumor&selectedTitle=1~2

.Updated May 29, 2018. Accessed June 7, 2018.

4. Adamski JK, Kelsey A, Brennan B. Inflammatory myofibroblastic tumors following the treatment of malignancy in childhood: case reports. 

5. Gal AA, Koss MN, McCarthy WF, Hochholzer L. Prognostic factors in pulmonary fibrohistiocytic lesions. 

6. Hirabayashi K, Zamboni G. IgG4-related disease. 

7. Nakanuma Y, Ishizu Y, Zen Y, Harada K, Umemura T. Histopathology of IgG4-related autoimmune hepatitis and IgG4-related hepatopathy in IgG4-related disease. 

8. Coates TD. Infectious causes of neutropenia. UpToDate.com. Available at: 

https://www.uptodate.com/contents/infectious-causes-of-neutropenia?source=search_result&search=viral%20induced%20neutropenia&selectedTitle=1~150

. Updated August 16, 2016. Accessed June 7, 2018.

9. Segel GB, Halterman JS. Neutropenia in pediatric practice. 

10. Bux J, Behrens G, Jaeger G, Welte K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. 

11. Farruggia P, Dufour C. Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians. 

12. Teachey DT, Lambert MP. Diagnosis and management of autoimmune cytopenias in childhood. 

13. Cojean N, Blondet C, Marcellin L, et al. Successful stem cell transplantation in an infant with severe congenital neutropenia complicated by pretransplant inflammatory pseudotumor of the liver. 

Articles

A 7-month-old girl presents to her pediatrician’s office with a 1-week history of fevers and upper respiratory symptoms. What's the diagnosis?

Infant with febrile neutropenia and a hepatic mass

New mothers may develop postpartum depression (PPD) at any time during the first year after giving birth, an analysis of monthly depression screening data showed. Furthermore, the highest rate of positive screens-23%-was at 12 months postpartum.

Investigators screened 152 new mothers for PPD every month for a year after they gave birth using the 10-question Center for Epidemiological Studies Depression Scale (CES-D-10). During the study period, 49% of participants had a positive PPD screen during at least 1 month. Of those who screened positive, 17% had their first positive screen at 1 month, 8% at 2 months, and 6% at 6 months. An additional 9% of mothers had their first positive screen after 6 months.

In other words, 15% of those new mothers who screened positive did not do so until 6 to 12 months postpartum. Analysis also showed that living in a household earning $50,000 or less and having a limited education increase the risk of a positive PPD (

The American Academy of Pediatrics recommends screening mothers for PPD at their child’s visits in the first 6 months of life. This study suggests that continuing beyond that date may be helpful. I am always struck by the thought of how many more times a mother is likely to see her child’s doctor than her own doctor in the year after giving birth. Pediatricians can be an important link to mental healthcare for mothers suffering with PPD.

How long are new mothers at risk for postpartum depression?

1. It’s okay to be silly during a visit (eg, trying to find where a child hid his or her belly button), as long as there are no serious health problems and it fits your style and the child’s. This is particularly effective with children aged between 3 and 6 years.

2. Similarly, when an older child comes in with mild poison ivy, besides asking them how many leaves poison ivy has, I ask what it feels like. The correct answer, of course, is that you are not supposed to know what it feels like.

3. Along these lines, I carry some simple magic tricks in my bag, which can be done even by a clumsy person (or, in current medicalese, a person with dyspraxia) such as myself.

. If the 2-year-old is chugging down a bottle of milk during a visit for fever, advise the parents that the bottle should be given up once the child is well.

5. Infants do not have sleep problems; parents do. I have never had an infant complain that his parents woke him up at night to feed him, and he wanted them to stop. Presenting it this way will show the parents that, if they want their older infant to sleep through the night, they will have to be the ones to bring this about.

6. Many parents are concerned that their normal child may have something wrong with him or her, or that they are doing something wrong, when the problem is actually due to the child’s temperament. I explain this as a matter of the child’s style, and that it is a question of personality, not pathology. There are many useful books on the subject for parents, but my shorthand description is that many children are either cats or dogs. The former, for example, are usually quieter, less demanding, and harder to read as to mood. The latter tend to be more intense, more engaging, and it is much easier to tell if they are happy/sad/excited.

Remember these simple pearls of wisdom. They will help you through each day with a smile and a happy heart.

6 pieces of old-school pediatric philosophy

When you approach a parent who is hesitant about vaccinating her infant at the appropriate well-baby visits, perhaps you say something like this: “Well, we have to do some shots.” Or you might say, “How do you feel about vaccines today?” The former strategy (a “presumptive” approach) is more likely to be effective than the latter (a “participatory” approach), according to a study in parents whom a standardized survey classified as being hesitant about vaccines.

Investigators assessed the immunization status of the newborns of 73 parents when the infants reached age 8 months. Using electronic immunization records, they obtained data from 82%, 73%, and 53% of participants after the 2-, 4-, and 6-month visits, respectively.

At each time point, clinicians used a presumptive approach more often than a participatory approach (65% vs 42%, respectively, at 1 or more visits). A minority of parents brought up the subject of vaccines themselves. The presumptive format at 1 or 2 or more visits was associated with increased immunization, and that association increased along with the number of visits at which this approach was used. The participatory format at more than 2 visits was associated with significantly more underimmunization, also in a dose-response relationship (Opel DJ, et al. 

The authors are not proposing that we should give vaccines without consent, but rather that you can lead a hesitant parent to consent more comfortably by projecting the expectation that she will want her child to be vaccinated. It turns out that the spin is important.

Parents are most likely to accept vaccines when you assume they will

The worried mother of an 11-year-old boy arrives at the office for evaluation of an asymptomatic bumpy rash that appeared suddenly in his right groin a month ago, and that has now extended all the way down to his right ankle. 

Lichen striatus (LS) is an uncommon, benign, self-limited papular eruption that follows the lines of Blaschko. It is a condition found most commonly in young children and that favors females.

 Three morphological patterns are described: typical lichen striatus, lichen striatus albus, and nail lichen striatus.

Nail lichen striatus is the least common. It occurs almost exclusively in children, and is usually restricted to a single nail.

 Lichen striatus albus is characterized by hypopigmented lesions. By far the most common morphology is typical lichen striatus, in which crops of tiny 1- to 2-mm scaly erythematous or flesh-colored flat-topped papules appear abruptly without any known trigger. The lesions are usually solitary and unilateral and most commonly involve the limbs.

 The patient is typically asymptomatic, but a minority may complain of pruritus.

 The eruption reaches maximum development over a few weeks and then self-resolves in 6 to 24 months. The only long-term sequela is postinflammatory hypopigmentation, which is seen more commonly in dark-complexioned individuals.

Although viral infections, trauma, hypersensitivity reactions, vaccines, medications, and pregnancy have been suggested as precipitators of LS, in the majority of patients triggering or causal factors are never found.

 It is thought that genetics and the environment contribute to the pathogenesis. The prevailing hypothesis is that genetic mosaicism provides the underlying substrate of LS.

 Early in development, a somatic mutation predisposes certain keratinocyte lineages to a currently unknown environmental insult. Basal keratinocytes present antigens from these unidentified environmental triggers to CD8+ T cells, leading to autoimmunity.

 Additional support for a genetic component comes from the fact that up to 85% of patients have a personal or family history of atopy.

In young children presenting with abrupt onset of erythematous papules in a Blaschkoid distribution, other linear lichenoid eruptions must be considered, such as linear lichen planus, lichenoid nitidus, lichenoid spinulosis, Gianotti-Crosti syndrome, chronic graft-versus-host disease, and frictional lichenoid eruption.

 The absence of pruritus, koebnerization, oral lesions, and systemic manifestations and the presence of postinflammatory hypopigmentation and nail dystrophy favor the diagnosis of LS.

Diagnosis is clinical, and biopsy is usually not necessary because LS is self-limited and histopathology is nonspecific with features of both eczema and lichen planus.

 However, for lesions that persist for longer than a year, a skin biopsy may be performed to differentiate LS from inflammatory linear epidermal nevi.

 This is important because one-third of patients with epidermal nevi have involvement of other organ systems, and there is a slight risk of malignant transformation.

 The classic biopsy finding in LS is a perivascular inflammatory infiltrate that is superficial and deep.

Because of the high likelihood of spontaneous regression, therapy is not required. The benign course of this dermatosis should be stressed to the parents. If treatment is desired because of pruritus or cosmesis, topical corticosteroids may be used. Some studies have shown these treatments hasten resolution, but this finding has not been consistently borne out.

A clinical diagnosis was made in this patient’s case with no further workup required. The family was reassured by the natural history of the illness. At a 6-month follow-up, the boy’s lesions had disappeared with only residual hypopigmentation.

1. Patrizi A, Neri I, Fiorentini C, Bond A, Ricci G. Lichen striatus: clinical and laboratory features of 115 children. 

2. Peramiquel L, Baselga E, Dalmau J, RoÃ© E, del Mar Campos M, Alomar A. Lichen striatus: clinical and epidemiological review of 23 cases. 

3. Tilly JJ, Drolet BA, Esterly NB. Lichenoid eruptions in children. 

4. Cohen BA, Davis HW, Gehris RP. Dermatology. In: Zitelli BJ, McIntire SC, Nowalk AJ. 

Zitelli and Davis’ Atlas of Pediatric Physical Diagnosis.

 6th ed. Philadelphia, PA: Elsevier Saunders; 2012:299-368.

5. Pickert A. Concise review of lichen planus and lichenoid dermatoses. 

6. Moss C. Mosaicism and linear lesions. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. 

. 3rd ed. Elsevier Saunders; 2012:ch 62, 943-962.

7. Goyal S, Cohen BA. Pathological case of the month. Lichen striatus. 

8. Weinberg JM. Epidermal nevi. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. 

Treatment of Skin Disease: Comprehensive Therapeutic Strategies

. 4th ed. Elsevier Saunders; 2014:204-207.

The worried mother of an 11-year-old boy arrives at the office for evaluation of an asymptomatic bumpy rash that appeared suddenly in his right groin a month ago, and that has now extended all the way down to his right ankle. What's the diagnosis?

Boy with red bumps all in a row

Researchers at Wisconsin Children’s Hospital in Milwaukee, Wisconsin, found that 100 children who visited a pediatric emergency department (ED) with a reported history of penicillin allergy based on low-risk symptoms all had negative allergy testing for penicillin and all tolerated a penicillin challenge (500 mg of oral amoxicillin) without developing a severe allergic reaction. Penicillin allergy labels were removed from these children’s hospital medical records. 

In a follow-up study to this one, conducted within a year after the negative results on standard 3-tier penicillin allergy tests were reported, investigators surveyed parents and primary care practitioners (PCPs) of each child to identify care practices and any subsequent antibiotic use or adverse events related to it. They combined data from the PCP and parent surveys to identify children who received an antibiotic and calculated financial savings for patients delabeled as penicillin allergic.

About 90% of parental respondents reported that they were aware of their child’s penicillin allergy testing results, while 84% of PCPs said that patient families had not notified them about the results. Indeed, about half the children still had a penicillin allergy label in the PCP medical record. Almost three-quarters of parents reported that they now would be “comfortable” or “very comfortable” if their child received a penicillin antibiotic. Those whose response was “somewhat comfortable” or “not comfortable” cited worry about a repeat allergic reaction to penicillin as the reason for their concern.

Delabeling children did change primary care and other physicians’ prescription behavior, however, with a total of 46 penicillin prescriptions for 36 study participants filled during the follow-up period. Amoxicillin or penicillin were the most commonly prescribed antibiotics followed by azithromycin, cefdinir, and combined amoxicillin and clavulanic acid. One child developed a rash about 24 hours after starting amoxicillin and was relabeled as penicillin allergic. No child had a serious allergic reaction after reexposure to the medication.

Investigators calculated that cost savings related to prescribing the penicillin-related antibiotics for these 36 children totaled $1368 and that cost avoidance amounted to $1812 in the interval since the first study (Vyles D, et al. 

One point of this follow-up study is to show that it is often difficult to delabel a child as allergic to penicillin. As this information is uncovered, it needs to be disseminated not only to the child’s providers in the medical home but also at urgent care centers, pharmacies, and other sites where he or she receives care. At least in this study, relying on the parents to carry this message proved unsuccessful.

I am eager for this group to publish results of prospective use of their penicillin allergy risk assessment survey. If it confirms their findings in the first trial, we may be able to “delabel” many children with soft histories of penicillin allergy.

Researchers at Wisconsin Children’s Hospital in Milwaukee, Wisconsin, found that 100 children who visited a pediatric emergency department (ED) with a reported history of penicillin allergy based on low-risk symptoms all had negative allergy testing for penicillin and all tolerated a penicillin challenge (500 mg of oral amoxicillin) without developing a severe allergic reaction. Penicillin allergy labels were removed from these children’s hospital medical records.

Is that child with "penicillin allergy" really allergic?

It is important for pediatricians to be aware that medical errors are frequent occurrences in pediatric practice. To safeguard our patients, we must implement an effective system to identify errors, as well as develop a strategy to prevent them.

The Institute of Medicine (IOM, now known as the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine) published the monograph 

 in 1999, alerting the medical community that medical errors were common in medical practice. According to the IOM report, “

at least 44,000 people and perhaps as many as 98,000 people die in hospitals each year as a result of medical errors that could have been prevented.

The monograph described and detailed the types of errors seen in the hospital environment. These included:
1. Diagnostic errors resulting from a failure to employ indicated tests or failure to act on the results of such tests.
2. Treatment errors in the performance of a procedure or administering of a treatment including medications, or inappropriate care.
3. Preventive errors, including failure to provide prophylactic treatment or inadequate follow-up to treatment.

The IOM report indicated that effective reporting systems needed to be implemented in healthcare facilities in order to reduce medical errors.

Whereas errors are common in the inpatient setting, the number of pediatric hospitalizations pales in comparison with the number of pediatric ambulatory visits each year. In 2015, the Agency for Healthcare Research and Quality (AHRQ) reported 5.6 million pediatric hospitalizations in the United States, while the Centers for Disease Control and Prevention (CDC) reported 125 million ambulatory pediatric visits that year.

The 2003 Learning from Errors in Ambulatory Pediatrics (LEAP) study conducted by the AHRQ and the American Academy of Pediatrics (AAP) Pediatric Research in Office Setting Network produced interesting data relating to the incidence of errors occurring in the ambulatory pediatric setting. In the 4-month data collection period from 14 sites, 136 errors were identified. Error types were: 37% medical treatment, 22% patient identification, 15% preventive care, 13% diagnostic testing, and 8% patient communication.

One of the authors of this article, Daniel Neuspiel, MD, initiated a quality improvement project in 2008 for Myers Park Pediatrics, an affiliate of the Levine Children’s Hospital of Carolinas Medical Center in Charlotte, North Carolina. The project established a safety team that included front office staff, medical providers, nursing staff, and administrative personnel. The team developed a

 to identify errors in need of evaluation, using the reporting form in Figure 1. The team met monthly to review reports of errors, and recommended interventions that would prevent future errors.

Errors were defined as “any event in the patient’s care which did not go as intended with either potential or real harm.” Over a 30-month period from 2008 to 2010, 216 errors were reported. These included errors in office administration (94); communication (40); medication or immunizations (45); and lab or diagnostic testing (37).

 The team used a problem-solving system called 

 to look at the potential causes of the errors. The analysis technique utilizes a cause-and-effect diagram to identify problems and propose solutions (Figure 2). Examples of common ambulatory pediatric practice errors along with solutions are shown in Table 1.

Children are at higher risk than many adults for medical errors because they have medical dosages based on weight, limited ability to communicate symptoms when young, and often their care is fragmented, provided by not only their primary care physicians, but by varying caregivers, specialists, and providers that are seen in walk-in clinics and emergency departments.

According to the Physician Insurers Association of America, from 2003 to 2012, errors in diagnosis accounted for 828 closed pediatric cases with an average indemnity of $414,455; medication errors accounted for 113 closed cases with an average indemnity of $207,916.

The most frequent medical error type in pediatric practice is the 

. Children are at higher risk for diagnostic errors due to the difficulty in eliciting their symptoms, particularly in infants and toddlers. Another frequent source of error is 

, especially home medication use. Children are at particular risk due to mistakes in measurement of liquid medications, multiple caregivers responsible for medication administration, adolescents who are self-medicating without adult supervision, and other factors.

Diagnostic errors are problematic in that solutions may require radical changes in our healthcare system. According to the National Academies’ monograph 

,” solutions may include more reliance on clinical decision support tools, utilizing teamwork more effectively, and improving healthcare education to sharpen diagnostic acumen.

 The monograph further suggested we develop a nationwide reporting and liability system that supports the diagnostic process and design a payment and care delivery model that encourages, rather than delays, patient visits.

According to a systematic review, as many as 10% of all pediatric medication orders result in a medication error.

 This topic was reviewed by author Andrew Schuman, MD, in the October 2017 issue of 

 (see “Safety first: How to avoid missteps when prescribing medications,” October 2017, page 38).

Providers can take a variety of steps to avoid prescribing errors (Table 2).

 We can distribute dosing charts to parents for over-the-counter medication and reinforce their use with verbal instructions. Providers must confirm the patient’s weight prior to writing a prescription and make sure the weight-based dose does not exceed the adult dose. In addition, prescriptions must indicate the exact dosage strength and the volume of medication to administer. Other measures that can reduce errors are using pediatric computerized order entry systems and standing order sets when available, and having an appropriate measuring device dispensed along with the medication.  Having caregivers explain back to you how they will administer the medication (

) and show you how they will measure it (

) are two techniques that have been helpful in reducing these errors.

There are a variety of common errors, other than diagnostic and medical errors, in medical practice that have been identified. Treating the wrong patient error is reduced by using 2 identifiers to confirm that the correct patient is being treated. Time-outs are appropriate means to reduce errors in the surgical suite. In the practice environment, electronic health records (EHRs) are often a cause of error as it is an easy matter to write the wrong note on the wrong patient and subsequently generate incorrect prescriptions. This common error can be avoided (but not eliminated) when providers take the time to confirm-twice-that they are in the correct record before writing prescriptions or documenting a visit. To make sure patients understand your recommendations, it is always a good idea to provide written instructions and have parents repeat instructions to you.

The Myers Park Pediatric Error Reduction Project, described above, created a safety model that will work in most ambulatory pediatric settings. One needs to acknowledge that errors are frequent occurrences in pediatric practices. However, errors can be reduced and prevented by creating a multidisciplinary safety team.

Nonpunitive reporting improves the detection of even minor errors. The team meets regularly to review reporting forms, discuss errors, and develop solutions that are tested. If successful, these processes become office policy, but if unsuccessful they are reevaluated.

By implementing these few measures, you will create a safer environment for your practice and your patients and cultivate a “culture of safety.”

To Err Is Human: Building a Safer Health System

. Washington, DC: National Academies Press; 2000.

2. Mohr JJ, Lannon CM, Thoma KA, et al. Learning from errors in ambulatory pediatrics. In: Henriksen K, Battles JB, Marks ES, Lewin DI, eds. 

Advances in Patient Safety: From Research to Implementation (Vol 1: Research Findings)

. Rockville MD: Agency for Healthcare Research and Quality; 2005:355-368.

3. Neuspiel DR, Stubbs EH, Liggin L. Improving reporting of outpatient pediatric medical errors, 

4. National Academies of Sciences, Engineering, and Medicine. 

. Washington, DC: National Academies Press; 2015.

5. Rinke ML, Bundy DG, Velasquez CA, et al. Interventions to reduce pediatric medication errors: a systematic review. 

6. Stucky ER; American Academy of Pediatrics Committee on Drugs; American Academy of Pediatrics Committee on Hospital Care. Prevention of medication errors in the pediatric inpatient setting. 

Diagnostic and medication errors frequently occur in pediatric practices, but even minor medical errors can be prevented by creating a culture of safety.

Prevent medical errors in your practice

When children present with recurrent infections, treatment of the specific infection is typically paramount in the clinician’s mind. While obviously necessary, such focus on resolving the infection may distract from considering an underlying condition, such as allergies or immunodeficiencies, that may be occasioning the recurrent infections.

“Some immunodeficiency disorders are not picked up as early as they might be because pediatricians are so focused on treating, for example, an ear infection from crisis to crisis with antibiotics that they may not get at the real cause, which might be an immunodeficiency,” says Stuart L Abramson, MD, PhD, FAAP, director, Allergy/Immunology Services, Shannon Medical Center/Shannon Clinic, San Angelo, Texas.

It is estimated that primary immunodeficiencies (PIs) occur in about 1:2000 live births.

 Unlike secondary immunodeficiencies that occur in connection with other conditions (for example, viral infections, malignancies, or malnutrition), PIs are inherited disorders affecting the functioning of the immune system. Children and adults with PIs are predisposed to infection, autoimmune disease and aberrant inflammatory response, and malignancy.

A key presenting feature of all immunodeficiency disorders is an increased susceptibility to infection. Therefore, children who present with frequent infections should be on the clinician’s radar as potentially having immunodeficiency disorders. This is the first step in recognizing and managing what could be a life-altering condition if not caught and treated early. Early diagnosis and treatment are critical to preventing or reducing the significant morbidity and mortality that can result if PIs are left undiagnosed and untreated.

“’Chance favors the prepared mind,’” says Abramson, quoting the French scientist Louis Pasteur. “If you don’t think about it, you aren’t going to make the diagnosis and help these patients. So just thinking about the problem, being alert to the early warning signs, and getting the proper testing and referral can make all the difference.”

In a presentation at the 2017 American Academy of Pediatrics (AAP) meeting in Chicago, Illinois, titled “

Recurrent infections: Is it immunodeficiency

?” Abramson discussed the warning signs suggestive of a PI, a stepwise approach to making the diagnosis, and management issues in the care of children with PI disorders.

Abramson opened his talk with a description of the different types of immunodeficiency disorders, focusing specifically on PI disorders. All PIs stem from the failure of one or more of the body’s defensive mechanisms to properly function. The type of PI depends on the specific defect of the immune system-whether it is characterized by a humoral (antibody) deficiency, cellular deficiency, or a combination of both humoral and cellular deficiencies.

Fifty percent of PIs are primary B-cell disorders: both more-common PIs (eg, selective immunoglobulin A [IgA] deficiency disorders) and uncommon PIs (eg, X-linked agammaglobulinemia). Other types of PIs are categorized as combined B-cell and T-cell immunodeficiencies (20%), phagocyte immunodeficiencies (18%), T-cell immunodeficiencies (10%), and complement immunodeficiencies (2%).

 Abramson provided a brief description of several common and uncommon PIs and their clinical presentations (Table 1).

To help clinicians recognize when a child may have a PI, Abramson referred to a quick checklist of 10 warning signs developed by the Jeffrey Modell Foundation.

 As noted in Table 2, a child who presents with 2 or more of these warning signs should undergo further assessment to make the differential diagnosis. Some of these symptoms also may indicate an underlying undiagnosed and untreated allergy, so making the correct diagnosis is crucial.

Abramson emphasized the importance of pediatricians knowing these 10 warning signs because “they are often the first line of defense in terms of picking up these patients and getting them to the proper specialists.”

Diagnosis of a PI disorder is based on stepwise approach involving 4 stages. Table 3 lists the stepwise approach to diagnosis recommended by the Jeffrey Modell Centers Network. Abramson said that most PIs (about 75%) can be diagnosed by obtaining a complete blood count (CBC) and quantitative immunoglobulin levels (stage 1).

If either test is abnormal, he emphasized, it is important to repeat the test to ensure that the first reading was not a lab error and that the positive test truly reflects a persistent problem.

“Unless you get a follow-up test, for example, of an initial test that showed either a low or high white blood cell count, you don’t know whether the blood cell count has normalized,” Abramson said. “In the case of a very low lymphocyte count that remains low, that could be indicative of a cellular immunodeficiency and not just a viral infection.”

“Viral infections can lower the white blood count, but if it doesn’t go away, it may be a persistent cellular deficiency,” he reiterated.

If a positive test persists after repeat testing, further diagnosis is indicated. For any diagnosis required after stage 1, Abramson suggests pediatricians consider referral to an allergist or immunologist for further workup. In addition to a potential diagnosis of a PI, some of these children with recurrent infections (eg, recurrent otitis) may have an underlying allergy that needs to be diagnosed or ruled out to make the correct differential diagnosis.

Following this stepwise diagnostic approach and referring children to specialists when warranted are critical to ensuring an accurate and early diagnosis.

“Early diagnosis is very important for some of these disorders because if the patient goes for a long period of time with recurrent infections, this can sometimes cause more chronic problems,” said Abramson, citing the potential for, among other conditions, the development of bronchiectasis if the underlying PI goes undetected and untreated.

In addition, Abramson said that early detection is critical for children who have a severe PI because they can be candidates for bone marrow transplantation. These children typically have an immunodeficiency that poses serious, life-threatening outcomes if immune reconstitution is not achieved. “If you wait too long and the infection becomes too difficult to treat or becomes chronic, it’s much riskier to do a bone marrow transplant because you have to immunosuppress the patient as you don’t want them to develop a graft-versus-host reaction,” he said. Characteristics for transplantation for PI disorder are listed in Table 4.

Currently, most children diagnosed with PI disorders are treated with immunoglobulin therapies that can be delivered either intravenously in the clinic or subcutaneously at home.

Table 5 describes a standard intravenous immunoglobulin therapy. For some children, subcutaneous therapy at home may be a better option. When compared with intravenous therapy, the benefits of subcutaneous therapy include improved quality of life, lower costs, and lower systemic adverse effects. However, disadvantages may include the need for more frequent treatments and local reactions at infusion sites.

Children presenting with recurrent infections may have underlying immunodeficiency disorders. Pediatricians should be alert to the warning signs indicating the potential for a PI disorder. Diagnosis includes a stepwise approach that begins with analysis of a CBC and quantitative immunoglobulin levels. If the results are positive after repeat testing, children should be referred to a specialist for further workup.

For most children diagnosed with a PI disorder, intravenous or subcutaneous immunoglobulin therapy is the standard treatment if specific antibody production is deficient.

Bone marrow transplantation is indicated for children with severe PI disorders. For all patients, early detection and treatment are critical to avoid long-term adverse effects of an untreated PI disorder.

1. Bonilla FA, Khan DA, Ballas ZK, et al; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and Joint Council of Allergy, Asthma, and Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. 

2. Modell V, Gee B, Lewis DB et al. Global study of primary immunodeficiency diseases (PI)-diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. 

3. Abramson SL. Recurrent infections: Is it immunodeficiency? F1120. Presented at: American Academy of Pediatrics National Conference and Exhibition; September 16-19, 2017; Chicago, IL.

For all patients with recurrent infections, early detection and treatment are critical to avoid the life-altering adverse effects of an underlying, untreated immunodeficiency disorder.

Vol 35 No 7