Dr Varsha v s, Dr Suma Balan, Dr Sajith Kesavan, Dr C Jayakumar
Five year old boy with past history of iron deficiency anemia, refractory to iron therapy requiring multiple blood transfusions presented with c/o cough of 2 weeks with shortness of breath and hemoptysis 2 episodes.
Past history Mother had Mixed connective tissue disorder on wysolone and azoran.
Normal perinatal period
Diagnosed to have iron deficiency anemia at the age of 2 yrs requiring multiple blood transfusions.
Development: Normal and immunized for age.
At admission he was sick looking with tachypnea and desaturation requiring low flow oxygen.
Labs done showed negative CRP, APTT, PT INR, URE were normal. Peripheral smear showing microcytic hypochromic anemia. Chest Xray done showed b/l patchy opacities. CT chest with contrast done showed b/l multiple irregular rounded and nodular alveolar densities of varying sizes and ranging from ground glass opacities to rounded consolidations s/o diffuse alveolar hemorrhage.
TB workup done was negative. In view of strong family history ANA IFA and complements were done and normal.
Echo done to r/o pulmonary hypertensionwas normal
Bronchoscopy was done to rule out any secondary causes.
After cardiac anesthesia clearance cryo lung biopsy was done which showed intra alveolar hemorrhage and hemosiderin laden macrophages with gamma gandy body like depositions.
Child was diagnosed with Idiopathic Pulmonary hemosiderosis and was managed with cyclophosphamide. He did not have further episodes of hemoptysis. He is kept on follow up
Discussion:
Idiopathic pulmonary hemosiderosis (IPH) is a rare lung disease characterized recurrent bleeding (hemorrhage) into the lungs without a known cause. This leads to the buildup of hemosiderin, an iron-storage complex, in the lungs. Over time, this accumulation can cause scarring, reducing lung function and leading to respiratory symptoms.
Symptoms:
o Chronic cough
o Shortness of breath
o Fatigue
o Hemoptysis (coughing up blood)
o Pallor or anemia due to blood loss, as the iron from red blood cells gets trapped in the lungs instead of being reused the body.
Pathophysiology:
The pathophysiology of idiopathic pulmonary hemosiderosis (IPH) involves complex interactions between lung tissue, blood vessels, and immune cells, though the exact mechanisms remain unclear. Pulmonary Hemorrhage, the hallmark of IPH is recurrent bleeding into the alveoli, the tiny air sacs in the lungs where gas exchange occur. Hemosiderin Deposition, blood entering the alveoli undergoes a breakdown, releasing iron from red blood cells. Macrophages (immune cells) in the lungs ingest the released iron, leading to the formation of hemosiderin, an iron-storage complex. Over time, this hemosiderin accumulates in the alveoli and lung interstitium (tissue surrounding the alveoli), visible as hemosiderin-laden macrophages on pathology.
Incidence: Idiopathic pulmonary hemosiderosis (IPH) is a rare disease, with an incidence estimated to be between 0.24 and 1.23 cases per million people per year.
Investigations:
1. Blood Tests
Complete Blood Count (CBC): Often shows anemia, which may be microcytic and hypochromic due to iron deficiency from chronic blood loss.
Iron Studies: Low serum iron, low ferritin, and elevated total iron-binding capacity (TIBC) indicate iron deficiency anemia.
Autoimmune Panel: Tests for autoantibodies (such as antinuclear antibodies or antineutrophil cytoplasmic antibodies) help rule out other autoimmune diseases like Goodpasture syndrome or vasculitis.
2. Pulmonary Imaging
Chest X-Ray: May reveal diffuse, bilateral lung infiltrates, often in a “patchy” or “ground-glass” pattern, indicative of alveolar filling. Findings may be transient, correlating with active bleeding episodes.
High-Resolution CT (HRCT) Scan: Provides more detailed imaging than an X-ray, showing ground-glass opacities or areas of lung consolidation. HRCT is useful in identifying fibrosis or interstitial changes that might occur with chronic disease.
3. Bronchoalveolar Lavage (BAL)
BAL involves washing out cells from a section of the lungs and examining them under a microscope. In IPH, hemosiderin-laden macrophages (macrophages containing iron deposits) are typically present, confirming alveolar hemorrhage.
BAL also helps rule out infection or other inflammatory conditions.
4. Lung Biopsy
Although invasive, a lung biopsy may be necessary if other investigations are inconclusive.
On histopathology, the biopsy shows hemosiderin-laden macrophages in the alveoli, with possible mild interstitial inflammation or fibrosis.
Biopsy helps confirm IPH when other causes of pulmonary hemorrhage (like vasculitis or connective tissue diseases) need to be ruled out definitively.
5. Pulmonary Function Tests (PFTs)
PFTs often reveal a restrictive pattern in advanced cases due to fibrosis and decreased lung compliance.
Diffusing capacity of the lungs for carbon monoxide (DLCO) may be elevated initially due to the presence of blood in the alveoli but may decline with progressive fibrosis.
6. Urinalysis
While not directly related to IPH, urinalysis is important for excluding other causes of pulmonary hemorrhage, such as Goodpasture syndrome, where kidney involvement (hematuria or proteinuria) is often present.
7. Echocardiography
Performed to assess heart function and exclude cardiac causes of pulmonary hypertension, which can occur secondarily due to chronic lung damage in IPH.
Management:
1. Corticosteroids
First-line Treatment: Corticosteroids are the mainstay of treatment for IPH.
Administration: Initial high doses (e.g., prednisone) are often used during active bleeding, followed a gradual taper to the lowest effective dose for maintenance.
2. Immunosuppressive Agents
For patients who do not respond adequately to corticosteroids or require long-term therapy with steroid-sparing effects, additional immunosuppressants are considered.
Common Immunosuppressants:
Azathioprine or Methotrexate: Commonly used to reduce the required dose of corticosteroids and control inflammation.
Cyclophosphamide: Used in severe cases but has a higher risk of side effects.
These agents help in achieving remission and reducing the frequency of bleeding episodes.
3. Iron Supplementation and Anemia Management
Oral or Intravenous Iron: Replenishes body iron stores and treats iron deficiency anemia due to chronic blood loss.
Blood Transfusions: Occasionally required in severe cases of anemia if iron supplementation alone is insufficient or if hemoglobin levels are critically low.
High-Resolution CT (HRCT) Scans: Periodic imaging may help monitor lung changes, especially in patients with progressive disease.
Blood Tests: Regularly assess for anemia, iron levels, and potential side effects of long-term steroid or immunosuppressive use.
Prognosis: The estimated 5-year survival rate for IPH ranges from 60% to 80% depending on disease severity and treatment response.
Complications:
Respiratory Complications
Chronic Respiratory Failure:
Pulmonary Fibrosis:
· Pulmonary Hypertension:
· 2. Systemic Complications
Iron Deficiency Anemia:
· Heart Failure:
· 3. Infections
Increased Susceptibility to Respiratory Infections
Opportunistic Infections: Prolonged immunosuppression can also predispose patients to opportunistic infections, such as fungal infections, which are more difficult to treat and can complicate the disease course.
4. Medication-Related Complications
Steroid-Related Side Effects: Long-term corticosteroid use is associated with osteoporosis, diabetes, weight gain, high blood pressure, and an increased risk of infections.
Immunosuppressant Side Effects: Drugs like azathioprine, cyclophosphamide, and methotrexate carry risks of bone marrow suppression, liver toxicity, increased cancer risk, and infection susceptibility.