Hyperferritinemia: Important Differentials for the Rheumatologists

Abstract

Ferritin is commonly used as a marker for iron status, aiding in diagnosing iron deficiency anemia. However, it is also an acute phase reactant often elevated in various inflammatory conditions. Marked hyperferritinemia, defined as ferritin levels above 10,000 μg/L, can indicate severe underlying conditions, including infections, cardiovascular like heart failure, endocrinological, autoimmune, and malignancies. This case report highlights the differential diagnoses and clinical implications of hyperferritinemia from a rheumatological perspective. Here are two case reports illustrating the use of ferritin in aiding the diagnosing of two uncommon conditions: adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The first case involves a 37-year-old male who presented with a pruritic rash, flu-like symptoms, joint pain, fever, and chills. Despite multiple emergency department (ED) visits, his hyperferritinemia reached 88,000 μg/L, and he met the Yamaguchi criteria for AOSD. Treatment with pulse-dose steroids led to a rapid resolution of symptoms. In the second case, a 50-year-old female presented with sepsis due to recurrent axillary skin infections, needing transfer to the intensive care unit. Laboratory findings revealed hyperferritinemia of 39,671 μg/L, crucial for distinguishing between rheumatological and hematological causes. Further investigation revealed diffuse large B-cell lymphoma. Tragically, the patient succumbed to her illness. The cases highlight the critical role of ferritin as a marker for underlying severe conditions. The clinical interpretation of ferritin levels and appropriate diagnostic workup are essential in identifying and managing these conditions to reduce morbidity and mortality. Ferritin levels should not be overlooked as merely an indicator of iron status or inflammation. Marked hyperferritinemia requires thorough investigation to differentiate between potential underlying conditions that may allow for more prompt recognition and management to reduce morbidity and mortality.

Keywords: adult onset still's disease (aosd); autoimmune diseases; hemophagocytic lymphohistiocytosis (hlh); hyperferritinemia; macrophage activation syndrome (mas).

Figure 1. Salmon-colored rash on the chest and back

Figure 2. Prevalence of common causes associated with various degrees of hyperferritinemia

The X-axis shows ferritin levels (μg/L), and the Y-axis shows various disease entities.