Goodpasture Syndrome - A Life-Threatening Autoimmune Disorder

Introduction

In 1919, Ernest Goodpasture described this disorder for the first time, and it is named after him. Goodpasture syndrome is an acute group of disorders characterized by autoantibodies directed against the basement membranes of the lungs and kidneys. It is believed to be of genetic origin, but the combination of other factors also plays a role in the pathogenesis of this condition. The symptoms aggravate as the disease progresses. Earlier diagnosis of the condition helps prevent further complications.

What Is Goodpasture Syndrome?

Goodpasture syndrome is a pulmonary-renal syndrome where the person’s own antibodies are directed against their lung and kidneys. This happens because the body's immune cells mistakenly start attacking the collagen that is present in the basement membrane of the kidneys and lungs. This eventually causes severe inflammation and destruction of the pulmonary and renal cells leading to failure of those organs. It is a serious fatal complication and needs to be addressed earlier.

What Is the Etiology of Goodpasture Syndrome?

It is an autoimmune disorder, and it is proposed to be due to environmental insults in persons with a genetic predisposition. Few studies report HLA-DR15 as a triggering stimulus in the production of autoantibodies against the glomerular basement membrane.

The environmental factors which act as an initial insult include,

• Smoking.

• Drugs such as Alemtuzumab.

• Cocaine inhalation.

• Viral infections.

• Exposure to chemicals such as organic solvents, hydrocarbons, etc.

What Is the Epidemiology of Goodpasture Syndrome?

It is more common in Whites than in the Black population, seen in younger men and older women. It shows bimodal age distribution, which is 20 to 30 years and 60 to 70 years, respectively, and accounts for one to five percent of all kinds of glomerulonephritis.

What Is the Pathogenesis of Goodpasture Syndrome?

Autoantibodies directed against the basement membrane will form antigen-antibody complexes, which, in turn, activate the complement system leading to tissue injury and inflammation. These bound autoantibodies are seen as linear deposition along the basement membrane, which can be visualized through immunofluorescence.

Why Do Pulmonary Symptoms Go Unnoticed?

In an otherwise healthy individual, the endothelium of the basement membrane acts as a barrier to these autoantibodies, preventing their binding with the alveolar basement membrane, which causes pulmonary symptoms. But in some cases, increased environmental insults such as smoking, upper respiratory tract infection, and bacteremia (a term that describes the presence of bacteria in the blood) can as well alter the barrier membrane leading to increased permeability, thus allowing the autoantibodies to enter and bind with the basement membrane leading to pulmonary symptoms.

What Are the Signs and Symptoms of Goodpasture Syndrome?

Initial symptoms include,

• Fatigue.

• Nausea.

• Fever.

• Breathing difficulty.

• Coughing up blood.

As the disease progresses, the following symptoms can occur,

• Anemia - Decreased red blood cell (RBC) count.

• Hematuria - Blood in the urine.

• Proteinuria - Protein in urine.

• Oliguria - Decreased urine output.

• Hypertension - Increased blood pressure.

• Cyanosis - Bluish discoloration of the skin and mucous membrane.

• Edema - Collection of fluid in the interstitial space.

How Is Goodpasture Syndrome Diagnosed?

A proper history of its symptoms and a heedful physical examination are imperative in the diagnosis of this disorder. The laboratory investigations include,

• Urine Analysis - To detect the presence of protein in the urine (proteinuria), presence of blood in the urine (hematuria), and red blood cell (RBC) casts in the urine.

• Blood Investigations - To check for antibodies (anti-glomerular antibodies) in the blood and anemia as a result of intrapulmonary hemorrhages.

• Renal Function Test - To detect renal malfunction.

• Chest X-Ray / Computerized Tomography (CT) Scan - To detect any pulmonary changes.

• Renal Biopsy - To check for histopathological signs of glomerulonephritis and to detect the antibodies against the basement membrane.

What Are the Histopathological Findings of Goodpasture Syndrome?

Microscopic examination of the renal biopsy will reveal the presence of glomerulonephritis. In the advanced stages, there will be fibrosis of the crescents followed by sclerosis. The interstitial stroma will show fibrosis and tubular atrophy. Immunofluorescence studies convey the linear deposition of IgG antibodies and complement along the basement membrane. The histopathological diagnosis will help in assessing the survival prognosis by identifying the number of crescents.

Lung biopsy is usually not indicated because of the complexity of the biopsy procedure as well as the difficult tissue fixation process. Microscopic examination of the lung tissue will reveal the presence of hemorrhage with hemosiderin-laden macrophages in the alveolar spaces.

How Is Goodpasture Syndrome Managed?

Treatment for this condition is based on certain factors such as the age of the patient, the severity of the disease, associated health conditions, etc. However, the general treatment protocol includes,

• Immunosuppressive Drugs - Drugs like Cyclophosphamide are prescribed to suppress the immune system from attacking the body's own cells.

• Corticosteroids - Drugs like Prednisone to reduce inflammation and stop bleeding from the lungs.

• Plasmapheresis - It is a process by which the plasma is separated from the blood, cleared off anti-glomerular antibodies, and replaced with healthy plasma. It is done daily until the anti-glomerular antibodies become undetectable in the blood.

In patients with severe presentation such as both glomerulonephritis and pulmonary hemorrhage, immediate hemodialysis and intubation for respiratory failure are suggested.

What Are All the Differential Diagnosis of Goodpasture Syndrome?

All the conditions that affect the kidney and lungs should be considered a differential

diagnosis. It includes,

• Systemic Lupus Erythematosus (SLE) - It is an autoimmune disease that affects the skin, lungs, heart, kidneys, etc.

• Microscopic Polyangiitis - This is a rare type of vasculitis that causes inflammation of the blood vessels.

• Wegener’s Granulomatosis - Rare disorder which is characterized by inflammation of blood vessels in the nose, kidneys, lungs, etc.

• IgA Nephropathy - This is a kidney disease in which IgA builds up in the kidneys leading to diminished kidney function.

What Is the Prognosis of Goodpasture Syndrome?

The prognosis of this condition has improved remarkably over the years because of the development of belligerent treatment therapies such as immunosuppressive drugs, corticosteroids, and plasmapheresis. The five-year survival rate is found to be 80 % after the introduction of these therapies. This array of diseases shows an overall good prognosis when it is diagnosed earlier and treated on time. The recurrence rate is very low, but possibilities of recurrence are reported.

What Are the Complications of Goodpasture Syndrome?

Complications such as decreased kidney function lead to kidney failure. 30 % of affected patients require long-term dialysis. In severe cases, renal transplantation is indicated.

Conclusion:

Goodpasture syndrome is a rare autoimmune disorder that may rapidly result in perpetual damage to the lungs and kidneys. It may be fatal if not quickly diagnosed and treated. Addressing the condition earlier and seeking medical help at a prompt time will help in preventing further damage to the tissues. With the introduction of advanced treatment modalities, the prognosis of this spectrum of disorders has increased drastically.