Pulmonologist perspectives regarding diagnosis and management of primary immunodeficiency diseases.

BACKGROUND: The time from symptom onset to diagnosis for patients with primary immunodeficiency diseases (PIDD) is an average of 12 years, but prompt diagnosis and treatment can promote best outcomes. OBJECTIVE: Because the manifestations of PIDD are often sinopulmonary in nature, patients with undiagnosed PIDD are frequently referred to pulmonologists. This study sought to identify opportunities among these specialists to improve diagnosis and clinical management of patients with PIDD. METHODS: A survey was sent to American Medical Association and American Osteopathic Association members whose specialty was pulmonology. Responses were compared with those from a historical survey of 71 subspecialist immunologists (American Academy of Allergy, Asthma Immunology members who devoted 10% of their practice to patients with PIDD). RESULTS: The surveys were returned by 485 pulmonologists, 49% of whom had diagnosed at least one patient with PIDD. In comparison with subspecialist immunologists, fewer pulmonologists were aware of the professional PIDD diagnosis and management guidelines and fewer followed up patients with various PIDDs. Pulmonologists and subspecialist immunologists also differed in the practice of prescribing prophylactic antibiotics and immunoglobulin replacement and in avoiding live viral vaccines. CONCLUSION: Differences in the diagnosis and treatment of patients with PIDD between these two groups of specialists revealed areas in which PIDD-focused educational initiatives may be helpful for pulmonologists.

Case report: Filamin A mutation lung disease recognized in an 11-year-old child.

The loss of function (LOF) due to mutations in the Filamin A (FLNA) gene may result in abnormality of the FLNA protein. Of the many clinical syndromes, this condition may produce chronic lung disease, which usually presents and is diagnosed in the infant/toddler age group. Its clinical pattern may mimic broncho-pulmonary dysplasia. It is part of the entities included in childhood interstitial lung disease group of disorders. We are herein reporting a patient that was diagnosed with FLNA-associated lung disease at 11 years of age. This case provides a unique insight into the long-term course of lung disease in this illness and broadens our understanding of the spectrum of its presentation. Although the patient had symptoms early in life, the diagnosis was not entertained because of the rarity of the disorder, its atypical and clinically mild presentation, and discontinuous care due to parents moving to different cities for employment reasons. Her presentation to our institution was for pneumonia. Due to highly unusual chest X-ray images, asthenia, and early clubbing, an extensive workup included further imaging and a lung biopsy. The final diagnosis was confirmed by the detection of FLNA LOF gene mutation.

Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome.

DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported. We found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients over the age of 3 years had hypogammaglobulinemia. We conclude that DiGeorge syndrome is associated with significant humoral immune deficiency.

A novel approach to the diagnosis and treatment of hemoptysis in infants: A case series.

INTRODUCTION: Hemoptysis in children is an uncommon presenting symptom but can be life-threatening if massive. Cardiac catheterization and coil embolization of aorto-pulmonary collateral vessels (APCs) is uncommon in pediatric hemoptysis patients without congenital heart disease. METHODS: We present a series of seven infants (≤12 months of age) with hemoptysis, all of whom underwent cardiac catheterization to look for and intervene upon APCs, if found. Only those patients who underwent both bronchoscopy as well as cardiac catheterization from January 1995 to January 2015 were included in this retrospective review. RESULTS: Seven patients met inclusion criteria, and three had a history of recurrent hemoptysis. The mean age was 3 months. Four had evidence of bleeding on bronchoscopy. All seven had respiratory distress which necessitated ICU admission; five required mechanical ventilation. Cardiac catheterization showed significant APCs (>2 mm) in six of the seven studied patients, all of which were coil embolized. One patient had no significant APCs and therefore, no embolization. All patients had complete resolution with no recurrences during the 10-20-year outpatient follow-up period. Chest CT scans were not helpful in delineating the site or etiology of bleeding in any patient. CONCLUSIONS: APCs should be considered as a differential diagnosis for pulmonary hemorrhage in infants after more common causes have been ruled out.

Autosomal Dominant Hyper-IgE Syndrome in the USIDNET Registry.

BACKGROUND: Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare condition. OBJECTIVE: Data from the USIDNET Registry provide a resource to examine the characteristics of patients with rare immune deficiency diseases. METHODS: A query was submitted to the USIDNET requesting deidentified data for patients with physician-diagnosed AD-HIES through July 2016. RESULTS: Data on 85 patients diagnosed with AD-HIES (50 males; 35 females) born between 1950 and 2013, collected by 14 physicians from 25 states and Quebec, were entered into the USIDNET Registry by July 2016. Cumulative follow-up was 2157 years. Of these patients, 45.9% had a family history of HIES. The complications reported included skin abscesses (74.4%), eczema (57.7%), retained primary teeth (41.4%), fractures (39%), scoliosis (34.1%), and cancer (7%). Reported allergic diseases included food (37.8%), environmental (18%), and drugs (42.7%). The mean serum IgE level was 8383.7 kU/mL and was inversely correlated to the patient's age. A total of 49.4% had eosinophilia; 56% were known to be on trimethoprim-sulfamethoxazole, 26.6% on antifungal coverage, and 30.6% on immunoglobulin replacement therapy. Pneumonias were more commonly attributed to Staphylococcus aureus (55.3%) or Aspergillus fumigatus (22.4%); 19.5% had a history of lung abscess; these were most often associated with Pseudomonas aeruginosa (P Fisher's exact test = .029) or A. fumigatus (P Fisher's exact test = .016). Lung abscesses were significantly associated with drug reactions (P χ2 = .01; odds ratio: 4.03 [1.2-12.97]), depression (P Fisher's exact test = .036), and lower Karnofsky index scores (P Mann-Whitney = .007). DISCUSSION: Data from the USIDNET Registry summarize the currently reported clinical characteristics of a large cohort of subjects with AD-HIES.

Hemoptysis from an aorto-pulmonary collateral vessel in a four month old resolved by embolization.

Hemoptysis in the children is a rare but serious diagnosis and is even more uncommon in infancy. Mortality is reported and depends on associated illnesses, underlying etiology, and amount of bleeding. A 4-month-old patient presented with significant hemoptysis. Flexible bronchoscopy with differential lavage confirmed the presence and site of origin of hemoptysis. She was managed with cardiac catheterization for embolization of an aorto-pulmonary collateral vessel with immediate complete resolution and no further recurrences. This highlights the importance of cardiac catheterization to detect collateral vessels as a cause for hemoptysis at this age and its successful resolution following embolization. Pediatr Pulmonol. 2016; 51:E31-E33. © 2016 Wiley Periodicals, Inc.

Long-term treatment of plastic bronchitis with aerosolized tissue plasminogen activator in a Fontan patient.

OBJECTIVE: To report the successful treatment of plastic bronchitis with aerosolized tissue plasminogen activator. DESIGN: Case report. PATIENTS: A 4-yr-old boy with congenital heart disease, who developed plastic bronchitis 33 months after a Fontan operation INTERVENTIONS: Long-term treatment with aerosolized tissue plasminogen activator. MEASUREMENTS AND MAIN RESULTS: We describe the case of a boy who developed recurrent episodes of life-threatening airway obstruction secondary to plastic bronchitis. Following the failure of multiple therapeutic interventions, his condition improved significantly with aerosolized tissue plasminogen activator. Several attempts to wean him off this treatment resulted in clinical deterioration. He has remained on long-term aerosolized tissue plasminogen activator. CONCLUSION: Treatment of plastic bronchitis with aerosolized tissue plasminogen activator may benefit patients in whom other therapies have failed.

Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency.

Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-α or anti-IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.

Ectopic subglottic thymic cyst: a rare cause of congenital stridor.

We describe the case of a 10-day-old boy who was brought to the hospital with stridor and respiratory distress. He was diagnosed with stenosis caused by a subglottic cyst. After the cyst was removed endoscopically, the patient's symptoms resolved. Pathology identified the cyst as ectopic thymic tissue. This case is noteworthy because we believe it represents the first reported instance of ectopic thymic tissue in the subglottis.

Juvenile xanthogranuloma: a rare cause of subglottic cyst and stenosis.

Only two cases of juvenile xanthogranuloma of the larynx have been previously reported in the literature. We report a new case, which occurred in an 18-month-old girl. The patient was brought to us for treatment of stridor and respiratory distress. During examination, she was found to have a subglottic mass. The lesion was treated with laser microlaryngoscopy, which relieved the patient's respiratory distress and obviated the need for tracheotomy. Pathologic examination of the mass revealed that it was consistent with a juvenile xanthogranuloma. Juvenile xanthogranuloma is generally a benign and self-limiting disease, but complications can occur when the space that the tumor occupies causes functional impairment.

Specificity and sensitivity of hemosiderin-laden macrophages in routine bronchoalveolar lavage in children.

CONTEXT: The presence of iron or hemosiderin in macrophages obtained in routine bronchoalveolar lavage is considered crucial in the diagnosis of the clinical syndrome of hemosiderosis. However, there do not appear to be any data on the sensitivity and specificity of the finding of hemosiderin-laden macrophages (HLMs) in bronchoalveolar lavage in children. OBJECTIVE: To review data from bronchoalveolar lavage studies done in children to correlate the presence of HLMs with pneumonia and hemosiderosis and to determine what proportion of HLMs has the optimal sensitivity and specificity for the diagnosis of hemosiderosis. DESIGN: One hundred ten bronchoalveolar lavage specimens obtained via flexible bronchoscopy were reviewed retrospectively. The data collected for demographics, indication for the bronchoscopy, diagnosis of pneumonia, anemia, and bronchoscopy and bronchoalveolar lavage findings were compared between patients diagnosed with hemosiderosis and those diagnosed with other diseases. RESULTS: Six patients were diagnosed with hemosiderosis by clinical findings, lung biopsy, or autopsy. There were no statistical differences in pneumonia (P > .99), anemia (P > .99), or coughing (P = .08) between patients with hemosiderosis and other patients. Hemoptysis was the only symptom that was significantly different between the 2 groups (P = .04). The mean HLM index for patients with hemosiderosis was 56% +/- 16.17% and for other patients, 7.5% +/- 10.74% (P < .001). A HLM index of 35% gave a sensitivity of 1% and a specificity of .96%. CONCLUSIONS: These results confirm a strong association between HLM index and diagnosis of hemosiderosis in a pediatric population. Availability of this HLM index will result in accurate and timely diagnosis of pulmonary hemosiderosis, which may influence treatment and long-term prognosis.