Discussion:
Pulmonary hemorrhage in children can be insidious or can present acutely as an acute life-threatening event (1). The bleeding may be diffuse (alveolar) or focal (2). Diffuse alveolar hemorrhage (DAH) is a rare but potentially life threatening condition in children. (2). DAH occurs as a result of injury to the small vessels (capillaries, arterioles and venules) of the pulmonary circulation (3). Idiopathic pulmonary hemosiderosis (IPH) is a diagnosis of exclusion and includes diffuse infiltrates, anemia and alveolar hemosiderin-laden macrophages of unknown cause (3). Various hypotheses have been proposed to explain the pathophysiology of IPH including allergic, environmental, genetic and/or auto-immune processes (4). The differential diagnosis in time has expanded to include pulmonary capillaritis (PC) and idiopathic hemorrhage of infancy (AIPH). Pulmonary capillaritis was first described in the 1950’s and is thought to be an immune mediated disorder that targets cytoplasmic components of neutrophils. It is an inflammatory process involving capillaries and may present in isolation or as part of a disorder (1). DAH with pulmonary capillaritis can have many causes, with underlying defects in the alveolar-capillary bed, immune mediated lung injury or environmental and genetic factors (3). Autoimmune disorders that are associated with pulmonary capillaritis include Wegener’s granulomatosis, microscopic polyantiitis, Goodpasture’s Syndrome, and Systemic Lupus Erythematosis (SLE). There are also associated drugs that include propylthiouracil, retinoid acid and phenytoin (3).
In order to identify pulmonary capillaritis and differentiate it from IPH, a lung biopsy is required. It is important to differentiate the two in order to guide treatment. Isolated pulmonary capillaritis is a rare disorder with poorly understood etiology (1). Our patient with isolated PC was very interesting in the she had strong family history of autoimmune disease, particularly in females on her maternal side, however her rheumatologic work-up was negative. There is very sparse literature available regarding management of pediatric patients with PC, particularly refractory cases such as our patient. In 2004, a case series was published by Fullmer, et al (2) that identified 8 pediatric patients with pulmonary capillaritis, ranging in age from 1.5 to 12 years of age. Final diagnoses varied and one patient was diagnosed with isolated pulmonary capillaritis. Interestingly, this patient appeared more recalcitrant than many others with underlying disorders. Many of the other patients were reported as “resolved” following pulse and oral steroids. Other treatments included IVIG, cyclophosphamide, hydroxychloroquine and azathioprine. There was also a case report published in 2015 that described a 45 year old male with isolated pauciimmune PC who failed cyclophosphamide and was then successfully treated with rituximab (5). Our patient had 2 known relapses in her course, one thought to be infection- related (acute pneumonia) and one without notable underlying cause, however she did not initially receive IV pulse steroids, as treatment options were not well published. She currently remains in remission following a combination of rituximab, pulse steroids and IVIG, followed by maintenance therapy with azathioprine and an oral corticosteroid taper and a total treatment time of about 3.5 years with these medications.
Since pulmonary capillaritis and particularly isolated PC is such a rare disorder in children, publication of cases is vital in order to begin to detect a pattern of successful therapies.
References:
  1. Parris D, van Niekerk A, Jeevarathnum, AC et al. An approach to pulmonary hemorrhage in children. S Afr Respir J. 2017; 23(3):63-70.
  2. Fullmer JJ, Langston C, Dishop M et al. Pulmonary capillaritis in children: a review of eight cases with comparison to other alveolar hemorrhage syndromes. J Pediatr. 2005; 146(3):376-81
  3. Susarla SC and Fan LL. Diffuse alveolar hemorrhage syndromes in children. Curr Opin Pediatr. 2007;19:314-320.
  4. Taytard J, Nathan N, deBlic J et al. New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare cohort. Orphanet Jurnal of Rare Disease. 2013;8:161.
  5. Thompson G, Specks U and Cartin-Ceba R. Isolated pauciimmune pulmonary capillaritis successfully treated with rituximab. Chest. 2015;147(4):e134-e136.