The lethal sting of many rare and chronic illnesses is the myriad of comorbidities and complications they produce in a given patient. 

Sickle cell disease (SCD) is a well-studied, well-understood disease in which the sickling of erythrocytes results in an inadequate supply of oxygen to meet physiological demands in the body. In the United States, it disproportionately affects the African-American community and is associated with lifelong morbidity and early mortality. 

“While acute vaso-occlusive pain episodes are the hallmark of SCD, individuals with this condition experience numerous other debilitating and life-threatening comorbidities throughout their lifetimes,” Ramsey and colleagues wrote in PLoS One. 

Unless a disease directly results in death, it usually causes mortality by a sequence of events, involving the complex interplay between comorbidities and complications. As a result, conventional medicine plays “catch up” by putting out flames: reducing a complication here, treating a comorbidity there. Unfortunately, these efforts rarely produce the desired results and simply prolong survival until the body is inevitably unable to cope. 

A Long List of Comorbid Conditions 

Ramsey and colleagues sought to characterize the prevalence of comorbidities experienced by patients with SCD. They chose patients with SCD who were commercially insured. Their retrospective study included patients whose information could be garnered from the Truven Health MarketScan Commercial Claims and Encounters Database, which contains claims from over 115 million individuals across the country. 

The inclusion criterion of the study was that the patient had to make at least 1 inpatient claim or 2 outpatient/emergency claims for SCD between 2007 and 2008. Patients who did not fit this criterion or were of unknown age were excluded from the study. A total of 20,206 patients met the eligibility criteria. 

“To identify comorbidities, we searched inpatient, ambulatory, and [emergency department] claims records of the study population for ICD-9/10 codes indicating those comorbidities,” the authors of the study explained.

Read more about SCD etiology 

The research team reported that patients with SCD suffer from a long list of comorbidities, with many directly related to the disease. Among the most common comorbidities reported were vaso-occlusive pain (38.8%), infections (23.61%), acute chest syndrome (22.17%), fever (21.15%), cardiovascular disease including pulmonary hypertension (13.66%), and chronic lung disease (9.38%). 

The authors of this study also discovered that these comorbidities increase with age. In addition, they reported that many patients with SCD complained of unspecified fatigue, something that has a disproportionate impact on their quality of life. Fortunately, mental health awareness is on the rise, meaning that many patients with psychological issues were able to receive help. 

Pain Management Strategies in SCD

In recent years, there has been a concerted campaign to view pain as the fifth vital sign—a campaign that has achieved considerable success. This is because pain can often directly or indirectly reveal much information about a person’s acute condition and pinpoint either the source of the problem or the effectiveness of a treatment solution. 

Chronic pain, however, is a slightly different story. As we discuss the possible comorbidities and complications of SCD, we would be remiss to not discuss pain management—something that is of incredible importance to patients who often suffer from periodic vaso-occlusive crises. 

“Acute pain episodes are the most common complication of SCD,” Brandon and DeBaun wrote in Hematology/Oncology Clinics of North America. “Acute pain episodes are abrupt in onset, unpredictable and account for the majority of health care utilization for SCD.” 

Read more about SCD treatment 

There are a number of pain scores that can be used to understand a patient’s pain level, but in a clinical setting, these may be unnecessary, especially if the patient is in obvious acute pain. Generally, there are 2 ways to deal with pain in a patient with SCD: pharmacologic therapy and psychological management. 

When a decision has been made to refer a patient with SCD to pain management, the pain management team makes decisions regarding the choice of medication, frequency, route, and mode of delivery. The objective is simple: reduce pain without creating unnecessary side effects. For this purpose, patient-controlled analgesia is usually the pain control method of choice, since it gives patients autonomy on the level of pain medication received. 

Psychological management may be necessary if chronic pain results in adverse mental health conditions, such as depression and anxiety, which tend to worsen the overall experience of pain. A study involving patients with SCD reported that patients with depression reported pain on 71% of days compared to 49% for those without depression. Hence, psychological care may be necessary to reduce the overall perception of pain when complications occur. 

It is clear that the management of the comorbidities and complications of SCD requires careful attention, especially when it comes to managing pain. Sometimes a kind word or reassurance can help alleviate some of the suffering experienced by patients with SCD. Nevertheless, all remedies begin with the recognition of a malady in the first place; it is therefore vital that physicians are constantly aware of the complex interaction between comorbidities and pain that takes place in each patient. 


Brandow AM, DeBaun MR. Key components of pain management for children and adults with sickle cell diseaseHematol Oncol Clin North Am. 2018;32(3):535-550. doi:10.1016/j.hoc.2018.01.014

Ramsey SD, Bender MA, Li L, et al. Prevalence of comorbidities associated with sickle cell disease among non-elderly individuals with commercial insurance — a retrospective cohort studyPLoS One. 2022;17(11):e0278137. doi:10.1371/journal.pone.0278137