Bridget Boyd, MD

A previously healthy 2-year-old girl, born at term by cesarean delivery due to breech presentation, with an uncomplicated postnatal course, presented to the outpatient clinic with a chief complaint of 2 days of itchy, bilateral leg rash. Her mother stated that each of her daughter’s legs had 5 or 6 quarter-size “bruises,” which felt like “hard welts” and were warm to the touch; some were dark purple, and others appeared redder. According to her mother, the patient had no fever, upper respiratory symptoms, abdominal pain, vomiting, diarrhea, discolored urine, blood in stool, change in gait, weakness, or joint swelling. She was fully immunized and had had no respiratory illnesses or fevers during the previous month. Her oral intake, urine output, and ambulation were normal, and she was otherwise her active, playful self.

The patient had no sick contacts, known bugbites, or recent exposure to outdoor pool or reservoir water. She had traveled to Michigan 2 months prior for a camping trip, during which she ran around in fields and forested areas. After returning home, her father checked her for ticks and found none. She had no other recent travel.

The patient lived with her mother and father, with 1 dog in the home and no smokers. The patient attended daycare 3 days a week with 10 other children and did not take any medications.

The patient’s symptoms began 2 days prior to presentation, with worsening itching and rash on her bilateral lower extremities. Her mother stated that she initially thought that the girl had bruises on her shins from playing, but the bruises grew larger, more numerous, and warm to the touch. The parents applied eczema cream and ice packs, which slightly improved the rash. The patient’s father had recently put new sheets on the girl’s bed, so the parents wondered if the symptoms might be an allergic reaction to the material. The patient’s family history is significant for Hodgkin lymphoma in the mother, who is also concerned about a possible malignancy in her daughter.

On examination, the patient appeared well, with no fever and no acute distress. Her growth parameters were normal for her age. Her vital signs were all within normal limits. She had moist mucous membranes without petechiae or exudates and normal lips, tongue, gingiva, and dentition. She had no enlargement of or exudate on the tonsils, no lymphadenopathy, and no pallor or cyanosis of the skin, and her respiratory and cardiac examinations were benign. Her abdomen was soft, nontender, and nondistended, with no hepatosplenomegaly or masses. She had no swelling, deformity, or pain in her extremities. Her skin exam was significant for multiple raised, blanching, erythematous, nonulcerated, immobile nodules on her lower extremities bilaterally (Figures 1 and 2).

After initial presentation to the outpatient clinic, the patient was prescribed ibuprofen 7.5 mL every 6 hours and advised to rest and keep her legs elevated. Pediatric infectious disease was consulted for evaluation of erythema nodosum (EN), with abnormal laboratory results showing elevated WBC.

The infectious disease consult determined that the etiology of this patient’s EN was likely infectious, and additional laboratory tests were ordered. These tests included CRP to assess for worsening inflammation, lactate dehydrogenase (LDH) level to rule out malignancy, QuantiFERON-TB Gold to rule out tuberculosis, and

 antibodies to rule out that infection. The results, completed 3 days after initial presentation, were the following:

Uric acid: 3.5 mg/dL (normal, 2.6-6.4 mg/dL)

LDH: 198 units/L (normal, 220-462 units/L)

 antibodies, IgM: 1234 U/mL (normal, < 770 U/mL)

 antibodies, IgG: ­ 0.90 (normal ­ 0.90)

The initial differential diagnosis included several infectious and noninfectious etiologies that could account for the findings of the patient’s skin lesions and laboratory results (Box). Erythema nodosum is a type of skin inflammation that particularly affects subcutaneous fat, which typically results in painful erythematous nodules at the front of the legs below the knees. These lesions do not ulcerate and usually resolve without atrophy or scarring.

 Lesions typically appear red at onset and, after a few days, evolve into a deep purple color, which may appear similar to a deep bruise.

 These nodules may be preceded by fever, malaise, arthralgias, or upper respiratory symptoms, and joint swelling or pain may emerge at the same time the skin nodules do. Erythema nodosum can be the first sign of a systemic illness such as tuberculosis and other bacterial or fungal infections, inflammatory bowel disease, sarcoidosis, or cancer, although in many cases, no cause of EN can be found.

 The most common cause of EN in children is idiopathic, followed by infection, sarcoidosis, and use of antibiotic drugs.

 Among infectious etiologies of EN in children, the most common are streptococcal pharyngitis, 

, histoplasmosis, coccidioidomycosis, and 

Diagnostic evaluation of EN includes a comprehensive history and physical exam as well as a complete blood cell count with differential, ESR, and CRP level.

 An individual patient’s presentation might warrant further evaluation, including testing for streptococcal infection, chest radiography, stool cultures, or testing for infection with tuberculosis.

 Although EN is often self-limited, any identified underlying disorder should be treated appropriately. Pain from the lesions of EN can be treated with nonsteroidal anti-inflammatory drugs.

This patient’s initial presentation was most consistent with an idiopathic etiology. She lacked prodromal symptoms of fever, malaise, and arthralgias, and she had no preceding upper respiratory symptoms. The absence of fever, sore throat, and accompanying respiratory symptoms made it less likely that her EN was secondary to infection with 

. Additionally, she had no sick contacts or known exposure to tuberculosis-positive individuals. She received a QuantiFERON-TB Gold­ Plus test to rule out 

Her absence of gastrointestinal symptoms made it less likely that her skin findings were secondary to 

. Similarly, a negative family history of irritable bowel disease and lack of gastrointestinal disturbances pointed away from Crohn disease or ulcerative colitis as possible etiologies. The patient lacked any respiratory symptoms of sarcoidosis and denied abdominal pain, vision changes, fever, fatigue, or weight loss. Furthermore, her below-normal LDH levels effectively ruled out a malignant process, as elevated LDH is a well-known indicator of malignancy.

Recent case reports have indicated the possibility of EN in individuals with COVID-19 infections,

 but such cases have not yet been documented in children, and data are still emerging regarding dermatological manifestations of COVID-19.

Although this patient showed no respiratory symptoms or signs of systemic illness, her laboratory results were positive for 

 IgM, indicating a recent infection. Using this serological evidence of infection combined with her elevated inflammatory markers at presentation, it was determined that the most likely etiology of her EN was subclinical infection with 

 is a significant cause of upper and lower respiratory tract infection in both adults and children, constituting up to 40% of community-acquired pneumonias.

 Most infected individuals experience mild disease, which often resolves without complication. The most common symptoms of 

 infection in children include low-grade fever, cough, nausea/vomiting, and skin rash.

 is most prevalent in school-aged children, with studies showing that just 13% to 18% of infected children actually develop symptoms. Estimations indicate that among individuals infected with 

, 50% of adults and 20% of children are entirely asymptomatic.

In this patient, the only symptom of infection was dermatologic. Skin changes associated with 

 infection have been reported in up to 25% of cases.

 Skin findings range from mild erythematous maculopapular or vesicular rash to bullous purpuric lesions and even a Stevens-Johnson–like syndrome involving mucosal surfaces, known as 

Case reports of erythema nodosum (EN) in the context of 

 infection in children are limited. The first documented case was in 2001: A case series of 35 children with erythema nodosum reported that 3 of them had antibodies indicative of recent 

 infection. In these 3 cases, 1 child had respiratory involvement, 1 had associated fever, and the third had no other symptoms.

 In a later study by Aydin-Teke et al, 39 patients with EN were retrospectively evaluated, with streptococcal infections identified as the most common cause, and only 2 of those patients were identified as having 

 infection was diagnosed using IgM positive serology. The first systematic review of EN and 

 infection in children was completed in 2015 by Greco et al, which concluded that the pathogenesis of EN is not yet fully understood. The investigators noted that further clinical and immunologic studies are needed to better understand the connection between EN and 

Multiple diagnostic methods exist for the detection of 

, each with its own advantages and disadvantages. Molecular polymerase chain reaction (PCR)–based testing has high sensitivity, high specificity, and rapid results, usually available in less than 1 day. However, PCR assays are expensive, often requiring specialized equipment and expertise.

 Serology-based testing has lower specificity but costs less and can be done via commercially available kits. Serology testing may require multiple patient visits to collect acute and convalescent samples, as a single elevated 

 antibody titer may not be definitive for distinguishing between active disease and an asymptomatic carrier state.

Culture is rarely used to detect M pneumoniae infection because isolation of the organism can take up to 3 weeks and requires a specialized medium to grow.

 Additionally, cold agglutinin antibody titers are not recommended because the formation of cold agglutinins is neither sensitive nor specific for infection with M pneumoniae.

 In current clinical practice, serology and molecular testing remain the most commonly used methods for detecting M pneumoniae infection.

This case demonstrates the importance of serologic testing for 

 infection in the case of pediatric erythema nodosum, even in the absence of pulmonary symptoms or radiologic findings.

 infection is usually mild and self-limited, not warranting specific treatment. In cases of pneumonia due to 

 infection, the most widely accepted treatment in children involves macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin.

 has no cell wall, making ß-lactam antibiotics ineffective. Furthermore, macrolides have a more favorable adverse effect profile in children compared with alternative drugs such as tetracyclines and fluoroquinolones. In children who are nonresponsive to antibiotic treatment, treatment with additional corticosteroids has been shown to be effective.

 infection are rare in children but include development or exacerbation of obstructive airway disease and asthma, alveolar hemorrhage, and acute respiratory distress syndrome. Morbidity and mortality are higher in smokers or individuals with underlying health conditions.

The prescribed regimen of ibuprofen, rest, and leg elevation failed to improve the patient’s skin findings. Pediatric infectious disease consult resulted in evidence of recent infection with 

, which was subclinical. The patient never developed systemic illness, but the erythema nodosum continued, with a new lesion on the proximal medial-anterior left thigh 12 days after her initial skin symptoms began. She had no pain at the new lesion’s site and remained afebrile, with no gastrointestinal disturbances or respiratory symptoms.

She completed a 5-day course of azithromycin (10 mg/kg, day 1; 5 mg/kg, days 2-5) according to recommendations from the consulting infectious disease physician. Her parents were counseled that the leg lesions should continue to resolve on their own, but they should manage the child’s pain and swelling with ibuprofen and cold compresses as needed. The patient remained well with gradual improvement of the pretibial lesions. Approximately 6 months later, at her 3-year-old well child visit, the patient had normal skin findings with no reported recurrence of the erythema nodosum.

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Articles

A 2-year-old girl presents with an itchy, bilateral leg rash. Additionally, the child had several bruises that felt like "hard welts" and were warm to the touch. What's the diagnosis?

Lower-extremity nodules in a 2-year-old girl

A newborn boy born via normal vaginal delivery at 38.6 weeks gestation to a 33-year-old G5P2022 mother presented at birth with an asymptomatic 8-mm red, papulonodule with central crusting on the right cheek (Figure 1). Pregnancy had been complicated by maternal type 2 diabetes mellitus and obesity. Delivery was uncomplicated and the patient was otherwise healthy.

Mother was otherwise healthy and the pregnancy was uneventful. Medications that were used during the pregnancy included prenatal vitamins, insulin, ranitidine, and diphenhydramine. All antenatal ultrasounds, serologies, and labs were unremarkable. Mother reported no relevant personal or family history, specifically no history of herpes simplex virus (HSV) infection, other viral infections, leukemia/lymphoma, or immunodeficiencies.

Initial physical examination revealed a well appearing infant. The Apgar scales were 9, 9, and 9 at 1, 5, and 10 minutes respectively. Patient weighed 3485 grams, an appropriate weight for his gestational age. Vital signs were within normal limits upon delivery.

Skin examination revealed an asymptomatic, round, red, non-blanching, 8-mm firm papulonodule on the right cheek. The lesion had an erythematous base with no drainage or crusting on initial exam. Central crusting later developed on the first day of life. The patient did not appear bothered by the lesion. Physical exam was otherwise unremarkable.

The patient received all routine neonatal labs. Hemoglobin and hematocrit levels were within normal limits. He required 2 oral glucose gels prior to glucose normalization. Metabolic screens were within normal limits. At 24 hours of life, C-reactive protein and a complete blood count were drawn and returned with no abnormalities.

Ultrasound of the lesion of the right cheek demonstrated a heterogeneous, hypoechoic lesion with no evidence of increased vascularity. Pediatric dermatology was consulted for further evaluation of the lesion and performed a biopsy that revealed Langerhans cells with surrounding inflammatory cells and eosinophils (Figures 2 and 3). A cutaneous proliferation of CD1a, CD68, and S100 positive cells was also confirmed via immunohistochemical staining (Figures 4 and 5). Fungal cultures, aerobe-anaerobe cultures, and an acid-fast bacilli culture were negative. These findings were typical of cutaneous Langerhans cell histiocytosis.

The initial differential diagnosis included several infectious and noninfectious etiologies that could account for such a skin lesion (Table). Infantile hemangiomas were high on the differential, as these are the most common skin neoplasms presenting in infancy.

 These are benign vascular tumors with a prevalence of 4%-10% worldwide.1 Ultrasound imaging may demonstrate an increase in internal vascularity. Ultrasound of our patient on day 1 of life indicated no prominent internal vascularity, making the diagnosis of infantile hemangioma less likely. Moreover, the presence of a nodule at birth and uniform blanching erythema with central crusting would not be typical of a classic infantile or congenital hemangioma.

Langerhans cell histiocytosis (LCH) was another diagnosis considered as it has a variable clinical presentation. Manifestations of this hematologic disorder can range from single cutaneous lesions to multiple cutaneous lesions, and to a multi-organ disease. Skin involvement is present in 33% of patients and appearance can vary from dry scaly lesions to crusted vesicles and red papules.

 Biopsy confirms characteristic histologic and immunohistochemistry findings.

Biopsy is also critical to exclude other diagnoses such as congenital juvenile xanthogranuloma. This is a form of non-Langerhans cell histiocytosis which can present as subcutaneous masses with overlying skin changes, papules, or nodules that are erythematous at presentation and become yellow in color over weeks to months.

 These lesions vary from a few mm in diameter to over 3cm, and most commonly involve the head, neck, or trunk.

Leukemia cutis describes skin manifestations that arise as a result of an underlying leukemia. These lesions can also have a variable presentation including red or violet papules, plaques, nodules or hemorrhagic lesions.

 These lesions commonly appear after a diagnosis of leukemia has already been made, but may also appear before there is any involvement of the peripheral blood or any systemic symptoms arise.

 Approximately two-thirds of patients presenting with neonatal acute myeloid leukemia also present with skin lesions, but lesions may be limited to the skin and resolve without treatment. However, these patients usually have other findings including hepatosplenomegaly or a high systemic tumor burden.

 Confirmation of this diagnosis is also completed via skin biopsy.

Other potential etiologies include congenital sarcomas, such as rhabdomyosarcoma. These soft-tissue neoplasms can present as red or violaceous nodules if they metastasize to involve the skin.

 Additionally, extramedullary hematopoiesis, or a “blueberry muffin rash”, can also present as similar papules and nodules that can be the result of an underlying infection (often TORCH infections), hemolysis, or malignancy.9

An infectious etiology also cannot be ruled out when a newborn presents with an abnormal skin lesion. Neonatal HSV needs to be considered due to the high morbidity and mortality rates associated with this infection.

 Patients with neonatal HSV usually present with clusters of vesicles localized to the skin, eyes or mouth. Failure to treat could lead to disseminated disease or spread to the central nervous system.

 Cutaneous lesions can also be the manifestation of infections caused by the other congenital TORCH infections, 

Infection could suggest that there is an underlying immunodeficiency such as HIV, malignancy, or a white blood cell disorder. Our patient did not present with any risk factors for these conditions and lab values were reassuring. Additionally, the patient was not exposed to any risk factors that would alter the function of the immune system at this age including maternal illness, prematurity, immunosuppressive medications or inadequate prenatal care.

Langerhans cell histiocytosis has an incidence of 2.6-8.9 cases per million amongst children aged younger than 15 years, and a median age of diagnosis of 3-4 years.

 This disorder is characterized by proliferation of CD1a, S100, CD68, and CD207 myeloid dendritic cells and has a highly variable clinical presentation.

 Any organ system can be affected, thus requiring a comprehensive evaluation of affected patients. Commonly affected sites include the bone, skin, central nervous system, pulmonary, hematopoietic, and hepatobiliary systems.

Among patients diagnosed with LCH, 33% present with skin findings.

 Skin lesions usually present as ulcerated, red papules, as was seen in our patient, but may also appear pustular, vesicular, or petechial in nature.

 In infancy skin manifestations may also resemble other skin disorders such as erythema toxicum neonatorum, eczema, or seborrheic dermatitis. As a result, it is important to accurately diagnose this condition to ensure appropriate treatment.

A rare variant of LCH named congenital self-healing reticulocytosis has also been identified. This condition was first described by Hashimoto and Pritzker and presents at birth or within the first few weeks of life.

 Patients may present with brown to violaceous papules located anywhere on the body. As with classic LCH, these lesions can be single or multiple. It is thought that the true incidence of this variant is underreported because most of these lesions resolve without treatment within the first 3-4 months of life.

Although children with lesions isolated to the skin usually have a good prognosis, patients with LCH who have isolated skin involvement also have an excellent prognosis, however, close observation is still required.

 In 40% of patients with similar isolated cutaneous findings progression to multi system disease or reactivation was observed.

Initial evaluation of patients with LCH requires determining whether there is single or multisystem involvement. Recommended testing includes a complete blood count with differential, complete metabolic panel including liver function tests, and coagulation studies. Imaging assessment should include a skeletal survey, ultrasound of the liver and spleen, and chest radiography.

 Treatment can then be tailored to the individual patient and extent of their disease.

Treatment for LCH is dependent on the site affected and the number of lesions. For patients presenting with isolated skin involvement, surgical resection can lead to cure. If lesions are multiple then topical corticosteroids are first line therapy, with second line agents including topical nitrogen mustard, oral thalidomide, and oral methotrexate.

 Additional studies need to be completed to further assess the efficacy of second line treatment options.

If skin involvement is diffuse or there are signs of multisystem disease, a systemic steroid with vinblastine for 6-12 months is first-line treatment. For patients with organ involvement (spleen, liver, bone marrow) 6-mercaptopurine may also be added to this treatment regimen.

 Prognosis for patients who fail these first-line treatment options is typically poor, and salvage therapy is indicated in these situations. This includes treatments such as hematopoietic stem cell transplant or a combination of cladribine and cytarabine.

Recent research has been investigating the use of therapies targeting BRAF-V600E mutations. Patients with this mutation are more likely to have higher risk LCH or have increased resistance to treatment.

 Vemurafenib, a BRAF inhibitor, has been shown to be efficacious, however further studies are required to determine appropriate dosing and duration of therapy.

Current recommendations for follow up for patients treated for isolated skin findings include evaluation of the lesion every 2 to 4 weeks. This includes monitoring for any signs of progression to multisystem involvement. Once the skin lesions have resolved, follow-up is recommended every 6 months for at least 5 years.

The cheek lesion was excised by pediatric dermatology and our patient was evaluated by the pediatric hematology-oncology service. Initial skeletal survey to assess for bone involvement showed a calvarial lesion suspicious for LCH. Follow up whole body positron emission tomography scan was completed and showed no findings of bone or other multisystem involvement. As a result, systemic therapy was not indicated as the cheek lesion was previously excised. It was determined that the patient likely had the congenital self-healing reticulocytosis variant of LCH. The patient continues to follow with serial skeletal surveys and labs, and remains in complete remission.

Acknowledgements: The authors thank Dr Kumaran Mudaliar, MD; Dr Wendy Kim, DO; and Dr Natalie Kamberos, DO for their valuable contributions to this case.

1. Rotter A, de Oliveira Z. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. 

2. Krooks J, Minkov M, Weatherall A. Langerhans cell histiocytosis in children. 

3. Papadopoulou M, Panagopoulou P, Papadopoulou-Alataki E. The multiple faces of Langerhans cell histiocytosis in childhood: A gentle reminder. 

4. El Demellawy D, Young JL, de Nanassy J, et al. Langerhans cell histiocytosis: a comprehensive review. 

5. Oza VS, Stringer T, Campbell C, et al. Congenital-type juvenile xanthogranuloma: A case series and literature review. 

6. Martínez-Leboráns L, Victoria-Martínez AM, Torregrosa-Calatayud JL, et al. Leukemia Cutis: A report of 17 cases and a review of the literature. 

7. Gru AA, Coughlin CC, Schapiro ML, et al. Pediatric Aleukemic Leukemia Cutis: Report of 3 cases and review of the literature. 

8. Roberts I, Fordham NJ, Rao A, et al. Neonatal Leukemia. 

9. Manning JR, Lee DH. Uncommon Neonatal Skin Lesions. 

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 20th ed. Philadelphia, PA: Elsevier; 2016.

12. Collins A, Weitkamp JH, Wynn JL. Why are preterm newborns at increased risk of infection? 

13. Carlo WA, Ambalayanan N. High-risk pregnancies. In: Kleigman RM, Stanton BMD, St. Geme J, et al. 

14. Leung AKC, Lam JM, Leong KF. Childhood Langerhans cell histiocytosis: A disease with many faces. 

15. Hashimoto K, Pritzker MS. Electron microscopic study of reticulohistiocytoma: an unusual case of congenital, self-healing reticulohistiocytosis. 

16. Trung A, Ahmad RC, Jennings C, et al. Congenital cutaneous Langerhans histiocytosis with mixed cell populations. 

17. Lau L, Krafchik B, Trebo MM, et al. Cutaneous Langerhans cell histiocytosis in children under one year. 

18. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. 

19. Donadieu J, Bernard F, van Noesel M, et al. Cladribine and Cytarabine in Refractory Multisystem Langerhans Cell Histiocytosis: Results of an International Phase 2 Study. 

20. Heritier S, Emile JF, Barkaoui MA, et al. BRAF mutation correlates with high-risk Langerhans cell histiocytosis and increased resistance to first-line therapy. 

21. Kobayashi M, Tojo A. Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment. 

22. Morren MA, Vanden Broecke K, Vangeebergen L, et al. Diverse cutaneous presentations of Langerhans cell histiocytosis in children: a retrospective cohort study. 

A newborn boy born via normal vaginal delivery at 38.6 weeks gestation to a 33-year-old G5P2022 mother presented at birth with an asymptomatic 8-mm red, papulonodule with central crusting on the right cheek. What's the diagnosis?

 Red papulonodule with central crusting on a neonate’s cheek

A previously healthy 4-year-old male, born late preterm by urgent cesarean delivery with an uncomplicated postnatal course, presents to the outpatient clinic for a chief complaint of worsening cough over the past 5 months. He denies current fever, rhinorrhea, shortness of breath, diarrhea, or vomiting. His cough has been worsening in severity and frequency, and mostly occurs during the daytime. The cough does not worsen at night and does not interfere with the patient’s daily activities. The cough is nonproductive and is not exacerbated with activity or laying in the supine position. He does not have any sick contacts at home nor any history of recurrent viral upper respiratory infections.

The patient’s cough symptoms began 5 months ago when the patient was first seen in the emergency department (ED) for a viral upper respiratory infection (URI) and was prescribed Tylenol and ibuprofen. He was subsequently seen in the outpatient setting 2 more times for a persisting and worsening intermittent cough, where supportive care was recommended with a trial of Zyrtec, without symptomatic relief for the patient. Last week, he presented to immediate care for a 4-day history of cough, congestion, diarrhea and vomiting, and a 1-day history of fever. He was prescribed ibuprofen and supportive therapy for a presumed recurrent viral URI, and the majority of his symptoms resolved except for his cough, which continued to worsen and prompted evaluation at this visit.

On examination, the patient is a well-hydrated afebrile child in no acute distress. His growth parameters are normal for his age. His vital signs are all within normal limits, and he is saturating 98% oxygen on room air. He has moist mucous membranes without pharyngeal erythema or tonsillar exudates. He does not have cervical lymphadenopathy, pallor or cyanosis, and he is not tachypneic, wheezing, or in evident respiratory distress.

On auscultation, his lungs are clear bilaterally with good air movement, but bowel sounds are appreciated over his lower-right sternum. His abdomen is nontender, nondistended, with normoactive bowel sounds in all 4 quadrants.

During the patient’s visit to immediate care the previous week, urinalysis, rapid strep test, rapid influenza diagnostic testing, and a frontal chest X-ray to rule out pneumonia were obtained. Urinalysis was within normal limits, and both the influenza testing and rapid strep test results returned negative.

The frontal chest X-ray demonstrated evidence of clustered gas collections at the gastroesophageal junction. Lateral and frontal chest X-rays were repeated at this visit, along with a respiratory polymerase chain reaction (PCR) panel. Respiratory PCR results were positive for parainfluenza. Both lateral and frontal chest X-rays demonstrated large air-filled loops of bowel extending anteriorly from the right diaphragm to medial right lower hemithorax (Figures 1 and 2). Pediatric surgery was consulted for evaluation of the abnormal imaging findings.

Chronic cough in children is typically defined as a cough lasting longer than 4 weeks’ duration in a patient aged younger than 14 years.

 In 2 studies evaluating the etiologies behind chronic cough in children, the most common causes included upper airway cough syndrome (UACS), also known as postnasal drip; asthma and asthma-like symptoms; gastroesophageal reflux disease (GERD); and protracted bronchitis.

Recommended initial evaluation in a child presenting with chronic cough is chest radiography and spirometry, although empiric therapy is usually not recommended in a child with a nonspecific chronic cough.

For this patient, his first presentation was consistent with a viral URI, which appeared to be the precipitating event for his cough. While his cough persisted, this was thought to be a self-resolving postviral symptom or a recurrent viral URI. Of note, his viral respiratory PCR was positive for parainfluenza, which indicates that he did indeed have a viral URI at the time of presentation. A Morgagni hernia was detected incidentally on his chest X-ray for a workup of pneumonia when he presented to immediate care for a fever with chronic cough.

The patient’s worsening cough may have been exacerbated by his hernia contacting the pleura and pulmonary lining, which would have been already irritated from multiple viral URIs. Additionally, Morgagni hernias have been reported to present initially as repeated chest infections and gastrointestinal (GI) complaints,

 both of which were present in this patient. However, it is also a possibility that the cough worsened the extent of his hernia by increasing intraabdominal pressure and placing strain on the diaphragm.

Although imaging clearly demonstrated air-filled loops of bowel herniating through the patient’s diaphragm, imaging is not always definitive because the visualized bowel may vary in consistency. Oftentimes, further evaluation with a computed tomography (CT) scan is indicated to evaluate the extent of herniation and to rule out other causes such as a pericardial fat pad, lipoma, or mediastinal cyst.

Although in many cases patients are asymptomatic, surgery is recommended on initial diagnosis of a Morgagni hernia to preserve normal lung function and prevent acute complications such as bowel incarceration.

Congenital diaphragmatic hernia (CDH) occurs at a rate of fewer than 5 in 10,0000 births and is relatively rare compared with other potential etiologies of chronic cough. Most reported cases of CDH are Bochdalek hernias, which present via posterolateral defects in the diaphragm, whereas Morgagni hernias, which present anteromedially, are exceedingly rare, accounting for less than 5% of diagnosed CDHs.

 Interestingly, although cases of CDH classically present on the left hemisphere, Morgagni hernias frequently localize to the right hemisphere.

Whereas CDH typically presents postnatally as acute respiratory distress in the neonate, a small subgroup of patients with CDH present later in life and may be asymptomatic. Compared with Bochdalek hernias, Morgagni hernias are more likely to result in a delayed presentation and diagnosis.

 Also unlike Bochdalek hernias, Morgagni hernias are not associated with lung hypoplasia or pulmonary hypertension, and thus do not present with acute respiratory symptoms postnatally.

For patients with a delayed presentation of Morgagni hernia, common complaints included recurrent respiratory infections, nonspecific GI complaints, and failure to thrive. However, many Morgagni hernias are found incidentally on imaging.

 Acute symptoms such as neonatal respiratory distress and GI obstruction also have been reported.

 Morgagni hernias have been shown to be related to other congenital abnormalities, such as heart defects and chromosomal abnormalities.

Morgagni hernias occur when the septum transversum fails to fuse with the costal arches during embryonic development, leading to a defect known as the foramen of Morgagni or the sternocostal triangle, which lies retrosternal, anteriorly and medially adjacent to the sternal and costal diaphragmatic attachments. Loops of large bowel, small intestine, or omentum subsequently can herniate through this open defect. The best initial imaging modality to diagnose a Morgagni hernia is chest radiograph in the postnatal period and beyond, which will demonstrate loops of bowel in the thoracic cavity, and ultrasound in the prenatal period, which will reveal a mass in the fetal thoracic cavity accompanied by a mediastinal shift.

This case demonstrates the importance of a thorough physical exam, as not all diaphragmatic hernias present acutely or with obvious symptoms.

A previously healthy 4-year-old male, born late preterm by urgent cesarean delivery with an uncomplicated postnatal course, presents to the outpatient clinic for a chief complaint of worsening cough over the past 5 months. He denies current fever, rhinorrhea, shortness of breath, diarrhea, or vomiting. His cough has been worsening in severity and frequency, and mostly occurs during the daytime.

Bridget Boyd, MD

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