| Highlights |
• Pulmonary manifestations of connective tissue disease are often multicompartmental (eg, interstitial lung disease and airway disease). • Patients who present with interstitial lung disease on imaging should seek clinical evaluation for features of connective tissue disease. • HIV has been associated with lung infection, malignancy, chronic obstructive pulmonary disease, and pulmonary hypertension. |
The lung can accumulate damage in many multisystem diseases. The airways, parenchyma, vasculature, pleural membranes, and respiratory muscles may be variably affected by the same underlying systemic process.
Multicompartmental respiratory complications can be found, for example, in interstitial lung disease (ILD) and pleuritis in seropositive rheumatoid arthritis (RA). Treatment of the pulmonary consequences of systemic disease may be directed specifically at the lung, generically directed at the underlying process, or supportive in nature.
| Connective Tissue Diseases |
CTEs can occur as “pure” entities or overlapping syndromes where the clinical features include aspects of different entities (e.g., systemic sclerosis (SS) and Sjögren’s Syndrome). CTE-EPI is most commonly found in RA, SS and myositis. Patients with CTE-ILD are more likely to be female and younger than those with idiopathic PID. In recent years, the use of biological response modifiers ("biologics") has expanded from the treatment of underlying CTE to the treatment of lung disease.
> Systemic Sclerosis
The most common radiological pattern of SS-associated PID is non-specific interstitial pneumonia (NSIP). PID is the leading cause of SS-related death.
Esophageal dilation and dysmotility in this condition can promote reflux of gastric contents that will cause additional lung injury. Recognized therapies for SS-ILD include cyclophosphamide, mycophenolate, prednisolone, rituximab, and, more recently, nintedanib.
> Rheumatoid Arthritis
Fibrotic PID, pleural thickening or effusion, and pulmonary nodules represent the most common pulmonary manifestations of this disease. Airway pathologies, including bronchiolitis, bronchiectasis, and emphysema, may coexist with PID.
Evidence for the use of specific therapies in RA-ILD is lacking, but corticosteroids, cyclophosphamide, and mycophenolate mofetil have been used with variable effectiveness.
> Idiopathic Inflammatory Myositis (IIM)
This heterogeneous group of disorders includes dermatomyositis, polymyositis, and dermatomyositis or polymyositis-predominant disease along with circulating antibodies against aminoacyl-tRNA synthetase (forming anti-synthetase syndrome). PID can precede, accompany or follow the presentation of muscle disease.
Patients with IIM tend to respond well to immunosuppression, particularly with corticosteroids. Other treatments include mycophenylate, tacrolimus, and rituximab, a chimeric monoclonal antibody that targets the CD20 protein on B cells.
> Systemic Lupus Erythematosus (SLE)
In general, pleural involvement associated with SLE is more common than parenchymal lung disease. The term “lupus pneumonitis” describes an acute/subacute syndrome of lung injury associated with a high risk of mortality. Shrunken lung syndrome is also described in SLE, mainly characterized by ventilatory restriction.
> Primary Sjögren’s syndrome
Bronchiolitis, bronchiectasis and/or diffuse parenchymal abnormalities may develop. NINE is the most common described radiological phenotype; others include organizing pneumonia and lymphoid interstitial pneumonia.
> Mixed connective tissue disease
Mixed CTE is associated with anti-RNP antibody positivity and shares overlapping features of lupus, myositis, and scleroderma.
> Ankylosing spondyloarthrosis
In addition to ventilatory problems related to thoracic restriction, pulmonary fibrosis of the upper zone is recognized that can progress to apical bullous disease.
> Recurrent polychondritis
In relapsing polychondritis, chronic inflammation of the cartilaginous component of the larynx or tracheobronchial tree can cause its weakening, leading to collapse or fibrosis of the airway wall. Airflow obstruction (predominantly during expiration), stenosis in 25% of cases and a greater predisposition to bronchial infection occur and explain the morbidity and mortality of affected individuals.
| Vasculitis |
Diffuse alveolar hemorrhage is the most dramatic pulmonary manifestation of vasculitis.
Its most common identifiable cause is granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis. The pulmonary vasculitic nodules most frequently described in GPA have a tendency to cavitate and produce localized hemorrhages.
First-line therapies for vasculitis include agents with “remission-inducing” properties, such as intravenous corticosteroids, intravenous cyclophosphamide, and high-dose methotrexate.
| Sarcoidosis |
Sarcoidosis is a multisystem granulomatous disease with a predilection for the lung. In its acute presentation it typically affects younger patients and causes intrathoracic lymphadenopathy or pulmonary nodular abnormalities.
Chronic sarcoidosis progressing to pulmonary fibrosis occurs in up to one-fifth of all patients. In some cases, scarring of the upper lobes leads to the formation of cavities that can promote Aspergillomycetomas.
The mainstay of treatment is corticosteroids. Depending on the site and severity of the disease, methotrexate, azathioprine, and hydroxychloroquine are used as second-line agents.
| Hematological Diseases |
> Early and late pulmonary complications of bone marrow transplant
Early (<120 days) pulmonary complications of hematopoietic stem cell transplantation include infectious and non-infectious events. The latter are grouped under the term "idiopathic pneumonia syndrome" and are associated with 60-80% mortality.
> Sickle cell anemia
Attacks of wheezing and obstructive lung function may occur in the absence of asthma in patients with sickle cell disease. Acute thoracic sickle cell syndrome develops as a consequence of vaso-occlusive events in the pulmonary vasculature.
Oxygen administration, blood transfusion and analgesia constitute the basis of treatment.
> Secondary pulmonary alveolar proteinosis
Several myeloproliferative and lymphoproliferative disorders have been associated with pulmonary alveolar proteinosis, including myelodysplastic syndrome and chronic myeloid leukemia.
The management of these forms of pulmonary alveolar proteinosis lies in the treatment of the underlying hematological disease and, in severe cases, in therapeutic complete pulmonary lavage.
| Infectious diseases |
> Human immunodeficiency virus (HIV)
HIV infects CD4 T helper cells, leading to severe impairment of cell-mediated immunity and increased risk of opportunistic infection and malignancy. People with HIV are susceptible to pneumocystis, particularly when the CD4 count is <200/mm3, as well as other fungi (including cryptococcus, histoplasma, and Aspergillus), bacteria (including "common" varieties such as pneumococcus), and viruses (including cytomegalovirus). Coinfection of HIV with tuberculosis is common, particularly in underdeveloped countries.
Certain malignancies, particularly viral-associated forms, are more frequently found in HIV. For example, Kaposi sarcoma is a multisystem malignancy caused by the human herpes virus.
Finally, patients affected by HIV have an increased risk of developing pulmonary hypertension.
| Gastrointestinal diseases |
> Inflammatory bowel disease (IBD)
The pulmonary complication in Crohn’s disease and ulcerative colitis usually affects the airways, with suppurative bronchiectasis being the most common manifestation. Patients with IBD also have an increased predisposition to thromboembolic events, including pulmonary embolism.
> Hepatopulmonary syndrome
Cirrhotic patients may develop dilation of the pulmonary vasculature predominantly at precapillary and capillary levels. Consequently, patients with hepatopulmonary syndrome are hypoxic even at rest and appear cyanotic.
> Portopulmonary hypertension
Cirrhosis can also lead to increased vascular resistance in the lung bed, resulting in a condition indistinguishable from idiopathic pulmonary arterial hypertension. Patients with this complication have a very poor prognosis.
