Diffuse alveolar hemorrhage (DAH) is characterized by alveolar space bleeding in the lungs, which occurs secondary to disruption of the basement membrane at the alveolar-capillary junction[1]. This disruption occurs secondary to injury or inflammation of blood vessels in the lung, usually the alveolar-septal capillaries [1-2]. The clinical constellation consists of hypoxemic respiratory failure, diffuse radiological pulmonary infiltrates with hemoptysis, and anemia or a decrease in hematocrit. Several diseases are associated with DAH, including Wegener's granulomatosis, microscopic polyangiitis, Goodpasture's syndrome, connective tissue disorders, infections, toxins, antiphospholipid antibody syndrome, and neoplastic diseases. Neoplastic diseases are generally not considered early in DAH differential diagnosis. Although certain malignancies have been described previously, undiagnosed solid malignancies manifesting as DAH have rarely been reported, making this case unique [3,4,5]. On histopathological examination, three different patterns of DAH can be distinguished, reflecting differing mechanisms. The most common presentation is pulmonary capillaritis or medium vessel vasculitis, in which neutrophilic infiltration and pulmonary interstitial destruction are observed. Systemic autoimmune vasculitis presents with such a mechanism. Another mechanism involved in infections is bland hemorrhage, in which red blood cells extravasate into alveoli without any inflammation. A third mechanism is diffuse alveolar damage with alveolar septal edema and hyaline membrane formation along the alveolar spaces. Infections, radiotherapy, and organ transplantation, i.e., hematopoietic stem cell transplantation, have been associated with this pattern [2,4,6,7]. The clinical presentation of DAH may be acute, subacute, or of variable severity with repetitive patterns. Clinical suspicion of DAH should arise in the setting of hypoxemic respiratory failure with diffuse alveolar infiltrates and dropping hematocrit. Hemoptysis may manifest after a few hours or a few days, but it may not be observed in up to one-third of patients who present with DAH. Nonspecific symptoms such as cough, chest pain, dyspnea, and fever may or may not develop [1,2,4]. Underlying systemic symptoms may also provide a clue to the underlying etiology in many cases. Patient clinical history holds utmost relevance since it may provide clues like recent infection suggesting cryoglobulinaemic vasculitis or Henoch-Schoenlein purpura; drug use, e.g., an anticoagulant, nitrofurantoin, D-penicillamine, propylthiouracil, cocaine, amiodarone, or sirolimus; toxin exposure to insecticides, pesticides, or trimellitic anhydride; or comorbid conditions, e.g., systemic vasculitis, mitral valve disease, and solid organ or stem cell transplantation [2,4,7,8,9]. The diagnosis of DAH requires clinician recognition of clinical, radiological, laboratory, and histopathological features. Two clinically important goals are to establish a DAH diagnosis and identifying the underlying etiology. Complete blood cell counts, including anemia, leukocytosis, and elevated inflammatory marker levels, are typical hematological findings in the setting of DAH. Pulmonary lung function tests are difficult to perform in the setting of rapidly progressing hypoxia in DAH; however, pulmonary lung function tests are usually characterized by an increased diffusion capacity of the lungs for carbon monoxide (DLCO) and a decreased fraction of exhaled nitric oxide (FeNO) [1,2,4,7]. Computed tomography of the chest characteristically reveals patchy or diffuse, bilateral ground-glass opacities, often more centrally located and at the bases typically sparing the periphery. Interlobular septal thickening may also be observed as was observed in our case. Bronchoscopy typically shows progressive bloody return of bronchoalveolar lavage (BAL) samples. The BAL fluid stained with Prussian blue was used to stain hemosiderin-laden macrophages [1,2,4,7]. Alternative diagnoses of DAH include a variety of etiologies, such as localized pulmonary hemorrhage by bronchiectasis, infection, or a tumor. Pulmonary infections, e.g., viral pneumonia, Mycoplasma pneumonia, Pneumocystis jiroveci and toxoplasmosis, aspiration pneumonitis, acute eosinophilic pneumonia, and acute respiratory distress syndrome, can all mimic clinicoradiological features similar to those of DAH [4,7]. Diffuse leukemic infiltration, a feature of malignancy, may also be confused with DAH [2,6]. Treatment strategies for DAH depend upon the underlying etiology. Basic supportive care includes hemodynamic stabilization, oxygen supplementation, noninvasive or invasive ventilation if needed, discontinuation of offending agents, and coagulopathy reversal. Immunosuppressive agents and plasmapheresis are the main treatment modalities for cases where DAH is caused by autoimmune vasculitides. In noninfectious DAH patients, high-dose pulse systemic steroid therapy is typically recommended to control inflammation. Most experts recommend intravenous methylprednisolone at up to 500 mg every 6 hours for 4 or 5 days, followed by a gradual tapering to maintenance doses of oral steroids. However, lower doses have also been found to have similar efficacy.Our case did respond well to steroid therapy. Other immunosuppressive drugs that may be used in refractory patients who do not respond to corticosteroids include cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, and etanercept [1,2,4,7]. In patients with Goodpasture's syndrome or other vasculitis in which immune complex and immunoglobulin titers are very high, plasmapheresis is indicated. Recombinant-activated human factor VII seems to be a promising new therapy, but further evaluation is needed. Treatment recommendations depend on an accurate determination of disease severity. The European Vasculitis Study Group (EUVAS) has devised a clinically useful grading system in which the patient's disease is categorized according to the severity of organ involvement: limited, early, generalized, active, generalized, severe, or refractory. Early recognition and prompt diagnosis of diffuse alveolar hemorrhage (DAH) can be a challenging but decisive step toward decreasing the high mortality rate associated with this life-threatening syndrome. Patients with malignancy should be monitored and evaluated promptly when presenting with hypoxemia and hemoptysis and DAH should be kept as one of the possibilities as it is treatable and can lead to better outcomes if identified correctly.
