World Sickle Cell Awareness Day was Monday, June 19th. The day was created from international efforts to bring awareness to Sickle Cell Disease, with the goals of increasing public knowledge of the disease and enhancing an understanding of the struggle persons living with SCD go through every day. To celebrate this awareness day, we wanted to continue shining the light on Sickle Cell Disease (SCD), and specifically focus on one of its most common complications: Acute pain crises.
What is Sickle Cell Disease?
Sickle cell disease is a genetic disorder that disrupts the genetic coding for hemoglobin, the protein within red blood cells that carries oxygen to all tissues of the body. The result of this disruption is sickle hemoglobin, a distortion of hemoglobin into its characteristic sickle shape. There are a multitude of problems that arise because of the shape of sickle hemoglobin, namely increased adhesion ability (facilitates binding to endothelial walls) and rapid hemolysis which increases reticulocyte (or immature red blood cell) production and endothelial damage. All of this inevitably leads to the induction of inflammatory cascades throughout the body, which results in acute and chronic organ damage at the cellular and molecular levels.
There are multiple types of SCD (HbS, HbC or beta-thalassemia) depending on which specific genes are disrupted that code for hemoglobin. However, the most concerning aspect of SCD is the substantially heightened morbidity and mortality associated with it compared to the general population. In particular, average life expectancy in those with the disease is about 20 years less than the general population.
Its prevalence is fairly common, as an estimated 300,000 infants are born with the disease worldwide every year. The disease appears to be more common among those whose ancestors come from sub-Saharan Africa, South and Central America, the Caribbean, parts of the Middle East, and even some Mediterranean countries. There is even a theory around its prevalence in parts of the world where malaria is or was more common (an intriguing premise around evolutionary adaptation). SCD specifically affects about 100,000 Americans, where it occurs among 1 out of every 365 African Americans, and 1 out of every 16,300 Hispanic-Americans.
Complications of Sickle Cell Disease:
So, why is SCD associated with so much morbidity and mortality?
The answer, of course, lies within the pathophysiology of the disease itself.
As stated, there are two main problems associated with sickle-shaped hemoglobin proteins; adhesion and hemolysis. Due to the adhesive nature of these hemoglobin molecules and associated endovascular inflammation, blood vessels may become occluded (vaso-occlusion) which results in associated ischemia, the primary cause for acute pain crises, acute chest syndrome, and avascular necrosis. Cellular hemolysis directly influences the risks of stroke, pulmonary hypertension, priapism, and leg ulcers. Depending on the genetic variant, these manifestations may be more or less common.
While each component and manifestation has its own specific management strategy, there are some more general and overall medication therapies that are directed at controlling SCD as a whole. Hydroxyurea had been the traditional (and only) therapy approved by the FDA for adults and children with SCD for years, until 2017 at which time several additional drugs (crizanlizumab, L-glutamine, and voxelotor) were approved. Hematopoietic stem cell transplant is currently the standard of care for more severe forms of the disease. The mechanisms and evidence of such therapies are subject for another blog down the road.
Acute Pain Crises: How do we manage?
One of the most common, severe, and life disrupting complications of SCD are acute pain episodes, or acute pain crises. The pathophysiology of acute pain crises is a concept for a more in depth publication, however it is important to know that there is neuropathic and central pain involvement that primarily result from ischemic injury, endothelial inflammation, and tissue damage. While the symptomology can vary individual to individual, usually, fatigue and body aches occur 1-2 days prior to the pain crisis (the prodromal phase), with escalating pain symptoms (sometimes localized) that peak between 3-7 days after onset. Usually these crises will resolve after several more days following its initiation.
Remember, we are talking about severe pain, for the most part. Therefore, without objective lab values or signs to help diagnose, the standard of care when diagnosing pain crises is the PATIENT’S REPORT! This makes it all the more difficult when assessing, however there should be minimal hesitation when considering treatment.
Speaking of treatment, how do we treat such severe pain episodes? Where do we typically treat them?
Usually, management of acute pain crises requires emergency department or hospital care, as acute use of parenteral opioids with or without NSAIDs IS THE STANDARD OF CARE! Yes, OPIOIDS ARE THE FIRST LINE TREATMENT FOR ACUTE PAIN CRISES!! Plus, the more quickly they can be administered to quell pain, the better the outcomes. Specifically, guidelines recommend that the first dose of parenteral opioid analgesics should be administered within 1 hour of arrival to the ED.
LET US RE-ITERATE: OPIOIDS SHOULD BE ADMINISTERED WITHIN 1 HOUR FOR THESE PATIENTS!
The reason we must highlight this point is not only because of disruptions in care for patients with SCD over the past few years, mainly as a result of the 2016 CDC opioid prescribing guidelines, but because of various stigmas and stereotypes that still plague those suffering from these types of acute pain crises in general. Such stereotypes and stigmas have run rampant throughout American history, almost always resulting in harm to minority populations (African American patients in particular). In the case of pain specifically, biases around race (especially the myth that black patients experience less pain than whites) can result in delayed and inadequate pain relief, and worsened mortality outcomes due to deteriorated care (this extends well beyond SCD, as well). Terms like “drug-seeker” or “opioid-seeker” are sometimes used to describe those afflicted with acute pain crises; terms that are unprofessional, inhumane, and derogatory that have absolutely no place in medicine!
The laughable part about that is, yeah NO $%&* the patient might be seeking an opioid. IT’S THE DAMN STANDARD OF CARE!
Plus, as we all should know by now, various opioid related risks (which is really what the underlying fear is about) have nothing to do with ethnicity itself or the pigment of one’s skin.
So, please, let’s all try to check our own stigmas, biases, and prejudices at the door and treat the individual patient! And, when it comes to acute SCD pain crises, GIVE THEM A DAMN OPIOID!
The problem with funding?
The future of treating and potentially even curing SCD is fascinating and optimistic, especially with the research going into gene therapy and their potential implications in SCD.
However, traditionally, despite its prevalence in America, SCD still receives poor overall funding. I mean, federal funding comparisons to other disease states is a joke. Let’s compare federal funding for cystic fibrosis to that received for SCD, as one example. Federal funding per person with cystic fibrosis was almost four times higher than it was per person with SCD ($2807 compared to $812). This is despite the US prevalence of cystic fibrosis being around 30,000 people (compared to about 100,000 of those living with SCD).
Should we even begin to ask why we think there is this drastic of a disparity in funding? I think we all know the answer to that.
Bottom Line: Sickle Cell Disease
Sickle Cell Disease is a genetic disorder primarily effecting hemoglobin characteristics that results in several severe and life-disrupting manifestations that substantially increase morbidity and mortality compared to the general population. One manifestation in particular is acute pain crises that results in severe pain episodes, often requiring emergency department or hospitalized care. Despite the fact that opioids are the standard of care, first line treatment modality for acute pain crises in those with SCD (to be given within one hour of presentation), patients with SCD often are faced with barriers in receiving such treatment due to several biases, stereotypes, and a lack of understanding of the specific pathology underlying these types of painful episodes. We should all use World Sickle Cell Awareness Day as a reminder to continue to fight against stereotypes and various sources misinforming care for these patients. And, as always, we need to treat the patient as an individual, and believe their pain!