PNH – the chameleon of hematology

Due to the versatility and the individually variable occurrence of these symptoms, the disease that is to be discussed here has often been referred to as the "chameleon of hematology or internal medicine": Paroxysmal nocturnal hemoglobinuria, PNH for short.

Like its animal namesake, PNH camouflages itself well and therefore often remains undetected for a long period of time. Like other highly rare diseases, PNH thus carries an additional burden until a successful diagnosis is made: A helplessness of not being able to identify the present disease - on the part of the patient as well as the doctor.

Fortunately, once PNH is suspected, modern flow cytometric methods can be used to make a definite diagnosis. PNH is caused by a somatically acquired gene mutation in the hematopoietic stem cells: The mutation of the so-called PIGA gene results in blood cells that can no longer properly identify themselves on their cell surface and are therefore no longer recognized as endogenous by the complement system, an archaic part of the immune system. As a result, the mutated blood cells will be destroyed.

Since in particular the mutated red blood cells are sensitive to the complement system, PNH often leads to a pronounced hemolysis. The release of hemoglobin from the destroyed red blood cells, the erythrocytes, leads to a wide variety of clinical symptoms as well as the eponymous accumulation of hemoglobin in the urine, which leads to its conspicuously dark color. Contrary to earlier assumptions, this process does not only take place at night, but this coloring can be more intense in the early morning due to the concentration of urine at night. In addition, paroxysmal hemolytic crises can occur, which can be triggered by infections, for example.

Up to the time, 15 years ago PNH was treated exclusively supportively, with up to 35% of patients dying within five years of diagnosis. However, the development of a therapeutic approach to specifically inhibit the complement system was able to significantly improve this situation and help patients to achieve a normal lifespan. The quality of life of PNH-affected people with often high disease burden in the untreated situation, was also able to improve significantly as a result. Complement inhibition has also been further developed and has made it possible for PNH patients to integrate the treatment regimen even better into their everyday lives.

It therefore seems of crucial importance that extremely rare diseases such as PNH are recognized as early as possible, so that the necessary therapy can be initiated. It is therefore important for new patients or undiagnosed patients with such rare diseases that the general population and doctors are more aware of those rare conditions. By that, long periods of suffering before the diagnosis is made can be shortened and the risk for the occurrence of life-threatening events can be reduced.

SKC consulting has dedicated itself to supporting the market access of innovative medicines for patients with previously missing or insufficient therapy options and is particularly specialized in rare diseases that frequently cause devastating burden. With this article, on the occasion of Rare Disease Day on February 28th, we would like to make a contribution to making PNH better known - so that it does not remain the hardly to recognize chameleon it was described as.

Sources:

• Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253-8.
• Schrezenmeier H, Maciejewski JP, Roeth A, Araten DJ, Kanakura Y, Larratt L, et al. Analysis of Baseline Clinical Characteristics and Disease Burden in Patients Enrolled in the International Paroxysmal Nocturnal Hemoglobinuria Registry. 2017;130(Suppl 1):3488.
• Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. (DGHO). Onkopedia Leitlinie: Paroxysmale nächtliche Hämoglobinurie (PNH). 2019.
• Luzzatto L. Clonal Origin and Clonal Selection in PNH. Paroxysmal Nocturnal Hemoglobinuria: Springer; 2017. p. 197-213.