Results
A total of 54 children included in the study. The median time from onset
to diagnosis was 0.9 years ± 2.2 (0.25 months to 12 years).
Consanguinity (first/second/third degree cousin) between parents was
present in 26 patients. The brother of one patient died after an episode
of similar symptoms. The main initial manifestations of the patients at
diagnosis were as follows: cough (n=41, 75.9%), dyspnea (n=29, 53.7%),
hemoptysis (n=29, 53.7%). The classic triad of anemia, hemoptysis, and
pulmonary infiltration in imaging was found in 24 (47.1%). While
hemoptysis was initially observed in 29 (53.7%) patients, it’s
determined in 33 (61.1%) patients, including follow-up time. A total of
41 (75.9%) patients were initially misdiagnosed; the most common
misdiagnosis was iron deficiency anemia and pneumonia. The main
demographic, clinical, laboratory, and radiologic findings at diagnosis
are described in Table 1 and Table 2.
Records of hemosiderin-laden macrophages in BAL were found for 24
patients, and all were positive. Gastric aspirate from 42 patients was
examined for hemosiderin-laden macrophages, and 28 (66.6%) patients
were positive. Six patients had negative results in gastric aspirate,
although their hemosiderin-laden macrophages in BAL were positive. BAL
fluid was positive for the following microorganisms in eight patients:
coronavirus (n=2), parainfluenza type 1 (n=2), respiratory syncytial
virus, cytomegalovirus (n=1), Haemophilus influenzae (n=2), and
Klebsiella pneumonia (n=1). Five children underwent a lung biopsy, which
documented features of pulmonary hemosiderosis with no sign of
capillaritis. Thirty-seven patients received blood transfusions. Seven
patients also needed transfusions after diagnosis.
Thirty-seven patients with complete current information of recurrence
(as provided in telephone conversations) were further analyzed According
to the presence of recurrent episodes, patients were dichotomized into
recurrence-positive and recurrence-negative groups. The mean number of
recurrent episodes per child in the recurrence-positive group was 3.55
(1-15). As seen in Table 3, univariate analysis demonstrated that the
recurrence-positive group presented more frequently with hypoxia
(P=0.002). Patients with a history of transfusion before or at the time
of the initial diagnosis had significantly higher recurrence rates
(P=0.002). Multivariate regression analysis showed that the presence of
hypoxia at the time of initial presentation was a significant
independent predictor of recurrent episodes (P=0.027). Ten patients
reported that their recurrence attacks were triggered after upper
respiratory infections. Two patients reported a decrease in attack
frequency after the influenza vaccine. However, no seasonal relationship
was determined with recurrence attacks.
Immunoglobulin E level was elevated in six patients. Cow milk allergy
was evaluated in 36 patients with one or more of the following methods:
skin tests, radioallergosorbent test (RAST) for milk protein,
allergen-specific immunoglobulin E, and provocation test; five of whom
were allergic to milk. Two patients were considered as having Heiner
syndrome in the follow-up period. At least one antibody was positive in
19 of 54 patients. Autoimmune screening results are given in Table 4.
During the follow-up period, ANA positivity developed in one patient,
and antigliadin positivity disappeared in one other patient.
Only 16 patients were able to perform the pulmonary function test at the
time of admission; 24 patients were aged under five years, and the
remainder could not perform the tests due to acute disease conditions.
The pulmonary function test was normal in 10/16 patients. Four of them
had a restrictive pattern, and two had both restrictive and obstructive
patterns.
Among the 54 patients, one patient was diagnosed as having coeliac
disease after the initial evaluation. One patient had arthralgia at the
time of diagnosis and was diagnosed as having familial Mediterranean
fever three years later. One patient developed arthralgia three years
later and was diagnosed as having juvenile idiopathic arthritis. One
patient had hematuria, but the renal biopsy was normal without specific
abnormalities suggestive of Goodpasture syndrome. One patient had a
positive result for anti-glomerular basement membrane (GBM), but the
renal biopsy was normal. One patient with anti-GBM positivity was
diagnosed as having Goodpasture syndrome during follow-up.
Coombs-positive hemolytic anemia developed in one patient in the
follow-up period. One patient developed end-stage kidney failure due to
nephrotic syndrome 20 years after the initial diagnosis while she was in
remission for IPH (ANCA result was negative and biopsy not suggestive of
Goodpasture syndrome). Pulmonary hypertension was determined in three
patients during follow-up. Three patients were evaluated for COPA
mutations, and all were negative.
All children were treated with systemic corticosteroids on initial
diagnosis. The mean duration of the total prednisolone course was 22
(range, 0.75-72) months. Hydroxychloroquine treatment was started in
eight patients, cyclophosphamide treatment was started in four patients,
azathioprine treatment was started in two patients, and inhaled steroids
were started in 16 patients during the reduction of steroid treatment
doses. In six patients, steroid-related adverse effects were observed.
In two patients, treatment was discontinued due to steroid adverse
effects. The median recurrence time of attacks after cessation of
corticosteroid treatment was 6 (range, 2-30) months. Of the 54 treated
patients, seven died of pulmonary hemorrhage and/or respiratory failure.
One patient discontinued steroid treatment after two months and was lost
to follow-up. When the patient was contacted again, he stated that he
had been depressed and had stopped all treatments because he had gained
weight and developed hypertension after steroid treatment. Six years
passed since the patient stopped treatment and he had mild hemoptysis
every day and shortness of breath with effort. A new CT revealed
bilateral patchy infiltration areas with ground-glass appearance.
Thirty-seven patients with complete long-term follow-up and treatment
information were further analyzed. Patients were categorized into three
groups according to treatment response; good, partial, and poor.
Thirty-seven patients with long-term follow-up or current information
(as provided in telephone conversations) were included in this grouping.
There was no significant difference in terms of the age of diagnosis,
delay in diagnosis duration, sex, onset time of symptoms, consanguinity,
initial signs, radiologic findings, and PFT. There was a significant
relationship between the presence of hypoxia, transfusion history, ANA
positivity, and elevated transaminases at the time of initial evaluation
and treatment response, as seen in Table 5 and Figure 1.