Marchiafava-Micheli disease

Marchiafava-Micheli disease, also known as Paroxysmal Nocturnal Hemoglobinuria (PNH), is a rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells, bone marrow failure, and blood clots. This condition is named after the Italian physicians Ettore Marchiafava and Ferdinando Micheli who first described it in the early 20th century.

Overview

PNH occurs when mutations develop in the PIGA gene of one or more hematopoietic stem cells in the bone marrow. These mutations lead to the production of blood cells (red cells, white cells, and platelets) that are deficient in a surface molecule called GPI-anchor. This deficiency makes the red blood cells susceptible to premature destruction by the complement system, a part of the body's immune system. This destruction process is known as hemolysis and is predominantly nocturnal, which is reflected in the name of the disease.

Symptoms

The symptoms of Marchiafava-Micheli disease can vary widely among individuals but commonly include:

• Fatigue and weakness due to anemia
• Dark-colored urine, especially in the morning, due to hemoglobinuria
• Shortness of breath
• Blood clots, which can lead to life-threatening complications such as stroke or pulmonary embolism
• Abdominal pain
• Difficulty swallowing
• Erectile dysfunction in men

Diagnosis

Diagnosis of PNH involves a combination of clinical evaluation and laboratory tests. The most definitive test is flow cytometry, which can detect the absence of GPI-anchored proteins on the surface of blood cells.

Treatment

While there is no cure for Marchiafava-Micheli disease, treatments are available to manage symptoms and reduce the risk of complications. Treatment options include:

• Eculizumab (Soliris), a monoclonal antibody that inhibits the complement system, significantly reducing hemolysis and improving quality of life.
• Bone marrow or stem cell transplantation, which can be curative but carries significant risks.
• Supportive care, such as blood transfusions for anemia and anticoagulants to prevent blood clots.

Epidemiology

PNH is a rare disease, with an estimated incidence of 1-2 cases per million people per year. It can occur at any age but is most commonly diagnosed in adults in their 30s and 40s.

Prognosis

The prognosis for individuals with Marchiafava-Micheli disease has significantly improved with the advent of treatments like eculizumab. However, the disease can still be life-threatening, and individuals with PNH require lifelong monitoring and care.