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:
- 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.
- 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
- Susarla SC and Fan LL. Diffuse alveolar hemorrhage syndromes in
children. Curr Opin Pediatr. 2007;19:314-320.
- 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.
- Thompson G, Specks U and Cartin-Ceba R. Isolated pauciimmune pulmonary
capillaritis successfully treated with rituximab. Chest.
2015;147(4):e134-e136.