Multisystem Inflammatory Disease with Respiratory Failure in a 7-Year-Old Boy

Relapsing polychondritis (RP) is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology. The estimated incidence is 3.5 cases per million. Of these only 10% affect pediatric populations.


Case Description
A 7-year-old African American boy was seen in the ED with respiratory distress, persistent left foot swelling, inability to bear weight, and worsening malaise for several weeks.Parents report a history of intermittent nasal congestion, noisy breathing with worsening hoarseness in voice, along with bilateral conjunctival injection worsening over two months prior to presentation.An outpatient workup for chronic rhinosinusitis included a CT of sinuses revealing a nasal mass, which was biopsied, and histopathologic results were pending on admission.
He was admitted for respiratory distress (physical exam revealed tachypnea, upper airway congestion, suprasternal retractions) and unexplained left foot swelling.Laboratory findings demonstrated increased inflammatory markers ESR 127 and CRP 21.Chest x-ray performed on presentation was normal.During hospitalization, he developed worsening respiratory distress and stridor requiring supplemental oxygen.Head/chest CT performed revealed a 5 mm subglottic airway narrowing with diffuse circumferential thickening of the subglottic airway wall and bronchus intermedius narrowing.Despite nebulized therapies and BiPAP, the patient de-

Introduction
Relapsing polychondritis (RP) is an extremely rare disease with estimated incidence of 3.5 cases per million, of which children represent 10% [1].First described in 1923, the peak incidence occurs in the 4 th to 6 th decades of life.RP is a presumed autoimmune, progressive inflammatory disease affecting multiple systems through recurrent inflammation and cartilage damage.As the respiratory tract is commonly involved, life threatening airway complications are concerning.Our patients' young age at onset with quick progression to respiratory involvement, along with time to diagnosis is unique.

Case Presentation
A 7-year-old African American male presented to the emergency department with worsening respiratory distress alongside inability to bear weight on left leg.Symptoms included general malaise, tactile fevers, intermittent epistaxis, noisy breathing, hoarse voice, and two month history of nasal congestion and worsening conjunctival injection.Outpatient workup for chronic rhinosinusitis included a CT of sinuses revealing a nasal mass, which was biopsied, with histopathology results pending on presentation (Figure 1).The constellation of symptoms including nasal chondritis seen on biopsy, laryngotracheobronchial involvement, and episcleritis seen by opthomologyalong with increased inflammatory markers, was suspicious for rheumatologic disease.
Testing including ANA, p-ANCA, c-ANCA, Anti-dsDNA, Anti-type II collagen Abs, IL-1 level, IL-6 level, TNFα level, and antiphospholipid antibodies were performed and negative.Results confirmed chronic arthritis for no other known cause.The constellation of these findings along with histopathology of biopsy and labwork, confirmed the diagnosis of relapsing polychondritis.
Child was started on mycophenalate 500 mg once daily and steroids 20 mg twice daily per rheumatology for multi-system inflammation with respiratory   He was extubated after initiating therapy (methylprednisone 30 mg/kg, mycophenalate 500 mg twice daily).Following extubation, he was placed on an airway clearance regimen of inhaled ipratropium (250 mcg) and manual chest physical therapy four times a day, and discharged on prednisone 2 mg/kg/day and mycophenalate 500 mg twice daily.
Within 2 weeks he re-presented to the ED with acutely worsening stridor associated with irritability/anxiety and cyanosis.Symptoms were refractory to racemic epinephrine, albuterol, and supplemental oxygen and he again required intubation.Repeat bronchoscopy revealed generalized subsegmental dynamic bronchomalacia worsening after suctioning.The degree of malacia was less compared to initial bronchoscopy though purulent secretions were greater with growth of 2 + Moraxella catarrhalis on lavage cultures.The decision for tracheostomy was reached based on history of multiple intubations secondary to upper airway collapse.Since tracheostomized, he has been stable from a respiratory standpoint on humidified room air, without further hospitalizations despite persistently elevated inflammatory markers.To address ongoing arthritis along with anemia and thrombocytopenia, our rheumatology team has treated with rituximab infusions, bi-weekly solumedrol infusions, low dose prednisone, methotrexate and naproxen.

Discussion
With lower respiratory tract involvement, mortality in RP increases to nearly 50%.Literature review found increased utilization of tracheostomy in pediatric patients with respiratory involvement [2].Respiratory chondritis (nasal or laryngotracheobronchial) is often asymptomatic earlier in disease.Patients often have cough, dyspnea, stridor, hoarseness, wheezing, and recurrent infections as the disease progresses [3] [4].Tracheal tenderness due to laryngotracheal inflammation is suggestive of RP, and laryngotracheal involvement is a significant cause of morbidity and acute or chronic mortality.
The mechanism of airway obstruction in RP initially includes inflammation resulting in airway narrowing in active stages.During progression, there is destruction of the laryngeal, tracheal, and bronchial cartilage with resultant dynamic collapse and formation of fibrous tissue causing cicatricial contraction [5] [6].
McAdam criteria are used for the diagnosis of RP and include at least three of the following: ocular inflammation, nasal chondritis, non-erosive seronegative inflammatory polyarthritis, audiovestibular damage, auricular chondritis or respiratory chondritis [7].
The and chlorambucil [10].New therapies may include immunomodulators like infliximab, etanercept, adalimumab, and abatacept as methods of better control.
Treatment of symptomatic airway disease includes continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or mechanical ventilation when tracheal collapse is present.

Conclusion
In

Figure 3 .
Figure 3. Flexible bronchoscopy identified severe malacia and thick secretions in the right upper lobe and mild malacia within the left upper lobe and lingula.(a) Thick Secretions; (b) Right upper lobe posterior segment malacia; (c) Apical segment right upper lobe malacia.
summary, though rare, pediatric relapsing polychondritis can present as a multisystem disease with airway involvement.McAdam criteria for diagnosis include at least three of the following: ocular inflammation, nasal chondritis, non-erosive seronegative inflammatory polyarthritis, audiovestibular damage, auricular chondritis or respiratory chondritis.The gorals of treatment for RP centers on control of inflammation with immunomodulatory therapy or immunosuppressants.When diagnosing suspected pediatric RP, evaluations should include complete assessment of upper and lower airways with consideration of noninvasive ventilation or tracheostomy to overcome airway obstruction.
differential diagnosis for RP is broad and consists largely of rheumatologic conditions such as Granulomatosis with Polyangiitis, Sarcoidosis, Rheu-G.Phull et al.Reactive arthritis, Polyarteritisnodosa, and Behçet disease.In this case, the child had ocular inflammation, nasal chondritis, non-erosive inflammatory polyarthritis for no other known cause, and respiratory chondritis.