Raynaud’s Disease and Sickle Cell Disease

Recent epidemiological studies suggest that episodic vasospasm of arterioles, also known as Raynaud’s phenomenon, and sickle cell disease are predominant in the general population. Raynaud’s disease results in a reduced blood flow to the fingers, and extraordinary cases, to the knees, toes, ears, nose, or nipples. Such happens because of spasms of blood vessels in the regions in response to emotional stress or cold. The peripheral Raynaud’s phenomenon/disease (RP) can be primary, abbreviated as PRP, occurring without coexisting condition or disease. It can also be secondary (SRP), caused by underlying connective tissue disease (CTD) (Mavrogeni et al., 2017).

Sickle cell disease (SCD) is a hereditary disorder of the blood caused by hemoglobin S (HbS), a mutated form of hemoglobin. SCD emerges from the substitution of a single amino acid in the gene encoding the β-globin component. The red blood cells (RBCs) deformability is decreased with the deoxygenation of polymerized sickle hemoglobin. The altered erythrocytes can barricade the vasculature, leading to hemolytic anemia, occurrences of pain, organ injuries, and even premature death. Even though the basis of sickle cell disease is well described, the multifaceted mechanisms fundamental to vaso-occlusion (VOC) are not entirely explained. Early research with a rat mesocecum ex vivo perfusion approach or vitro adhesion tests discovered SS-RBCs (sickle RBCs) in the beginning and dispersal of VOC events through adhesive association with the endothelium. Following post-capillary venules, the adhesion of SS-RBCs of low-density and reticulocytes can cause trapping of more dense and older sickle RBCs, leading to decreased blood flow (Connes et al. 2016). The present paper explores Raynaud’s Disease and Sickle Cell Disease, including pathophysiology, signs and symptoms, diagnostic tests, treatment modalities, key theories or concepts concerning the conditions, and nursing care implications.

Pathophysiology of Raynaud’s Disease and Sickle Cell Disease Process

Pathophysiology of Raynaud’s Disease

 Raynaud’s phenomenon/disease (RP) is one initial episode in the pathophysiological flow, which causes sclerosis in systemic sclerosis (SSc). The disease is occasioned by regular, alterable vasospasms of digital arteries, small arterioles in the fingers, and sometimes toes, often activated by emotional stress or cold (Musa & Qurie, 2021). According to the vascular theory by LeRoy, the vascular dysfunction characterized by heightened vascular permeability and spasm caused by dysregulated contractile muscular vessel wall’s response are primary events pathophysiological cascade causing sclerosis in SSc, presenting Raynaud’s disease on the skin, but can also occur in other organs. Raynaud’s disease can be primary (idiopathic) or secondary, resulting from several underlying conditions, and pathophysiology varies between the two states. Secondary RP frequently occurs in SSc but can also be linked to other autoimmune disorders such as thoracic outlet syndrome, paraneoplasia, cryoglobulinemia, or dermatomyositis (Górska et al. 2017). Drugs such as interferon-α or vinblastine can also trigger RP. Clinically, secondary RP is differentiated from primary RP based on several factors, including later onset, in individuals above 30 years, the severity of the pain, certain complications, including ulcerations, and by symptoms of the underlying or coexisting diseases, including connective conditions for instance fibrosis in SSc (Mavrogeni et al. 2017).

Pathophysiology of SSc-related RP

In systemic sclerosis, secondary RP is the heralding or initial symptoms in most patients, about 90%, and causes overture in the pathophysiology of systemic sclerosis, setting the ground for the process causing sclerosis. Besides, the vascular alteration can also partially reflect vascular changes in other organs, allowing the study of pathomechanisms in systemic sclerosis (SSc). As such, an understanding of pathomechanisms of RP can enhance the treatment of RP and SSc. The imbalance between weaker vasodilatory and strong vasoconstricting events is key to the pathophysiology (Fernández‐Codina et al., 2018). The underlying pathomechanisms can either be intrinsic disorders of vascular smooth muscle or endothelial cells. They may also be extrinsic, comprising soluble mediators and neuro-regulation

Mechanism of Cold-Induced Vasculopathy

Both primary and secondary Raynaud’s disease (RP) exhibits an un-physiologically amplified contractile reaction to α2-adrenergic agonists and abrupt cooling. The cold-trigged vascular reactivity is shown to enhance the protein tyrosine kinase (PTK) ‘s activity, which can also be abolished by PTK inhibitor (genistein). However, researchers have not yet stated clearly which kinase phosphorylated proteins induce RP. The α2c-adrenergic receptor is the primary mediator for cold-triggered vasoconstricting signals to cutaneous arteries’ smooth muscle cells (Llamas-Velasco, 2017). The augmented reactivity even surpasses other endothelial dysfunctions in systemic sclerosis.

Pathophysiology of Sickle Cell Disease

SCD is an autosomal-recessive hereditary condition that impacts millions of people worldwide. About 43 million people are carriers of sickle cell mutation, and over 170,000 people succumb to the disease every year. SCD is caused by beta-globin chain mutation in the hemoglobin molecule. The resulting sickle hemoglobin polymerized when deoxygenated. Over the past eleven decades, since the sickle cell was discovered in 1910, scientists have described three major pathobiological processes that drive SCD: Hemoglobin S (HbS) polymerization and vaso-occlusion (Sundd, Gladwin & Novelli, 2019). Sterile inflammation is the most recent fourth pathway.

Sickle hemoglobin (HbS) Polymerization

The primary cause of clinical SCD is the intracellular polymerization of HbS occurring when SS RBCs (sickle erythrocytes) are partially deoxygenated under microcirculation’s hypoxic conditions. This causes the SS RBCs to become less deformable, ultimately resulting in incapacitating microvascular occlusions and hemolytic anemia, which are characteristics of sickle cell disease (Wandersee & Hillery, 2016). The βS-globin chains attached to different sickle hemoglobin tetramers bind together, hence hiding the hydrophobic motifs. The nucleation of the sickle hemoglobin polymer is initiated in the process. The HbS polymers grow rapidly, forming long fibers and increasing cellular rigidity, distorting the erythrocyte membrane, causing erythrocyte sickling, stress and energetic cellular failure, dehydration, and premature hemolysis (Sundd, Gladwin & Novelli, 2019). Such explains the pathophysiology of SCD through (HbS) polymerization.

Vaso-Occlusion

Vaso-occlusion, also known as blood vessel occlusion, causes ischemia, and the leading pathophysiology for vaso-occlusive crisis (VOC), acute systemic pain, and a condition for an emergency by SCD patients. Researchers have suggested a significant role of adhesive interactions of reticulocytes and erythrocytes with endothelial cells and inflammatory in promoting VOC in SCD patients (Sundd, Gladwin & Novelli, 2019).

Sign and Symptoms, Diagnostic Tests, and Treatment Modalities for RP and SCD

Raynaud’s Disease/Phenomenon (RP)

Raynaud’s Disease causes mostly fingers and toes to feel cold and numb when responding to stress and cold temperature. In RP, the digital arteries that supply blood to the skin become narrow, restricting blow flow to fingers and toes. Women are highly likely to experience RP than men. The disease is common in colder climates. Other symptoms of RP include changes in skin color when responding to stress and cold and prickly, stinging pain or numb feeling upon stress relief or warming. The affected skin area turns white, then blue during the RP attack, feeling numb and cold. Upon warming and blood circulation improves, the area turns red, throb, and swell.

Diagnostic Tests for RP

First, the medic will ask the patient about the symptoms and health history and do a physical examination. Tests are done to rule out other illnesses presenting the same signs and symptoms. Nailfold capillaroscopy is performed to differentiate between primary RP and secondary RP. If the physician feels that another condition such as connective tissue disease or autoimmune disorder is causing RP, a blood test is likely to be ordered, including:

Erythrocyte Sedimentation Rate. The test establishes the rate at which RBCs settle down to the bottom of a tube. A higher or faster rate than regular may signal autoimmune disease or underlying inflammatory.

Antinuclear Antibodies Test. The presence of antinuclear antibodies may signal stimulated immune systems, predominant in individuals with connective tissue illnesses or other autoimmune syndromes.

No blood test has proven to diagnose Raynaud’s disease. Hence, the physicians must conduct other tests, including those that help rule arteries’ disease, to identify conditions possibly linked to Raynaud’s disease.

Treatment for Raynaud’s Disease

Keeping warm and wearing heavy socks or gloves are often effective in managing mild symptoms of Raynaud’s disease. However, severe forms of the condition might necessitate medication. The doctor may prescribe Vasodilators or Calcium channel blockers to widen blood vessels and enhance blood floor subject to the cause of the symptoms. Vasodilators help relax the blood vessels and include nitroglycerin cream applied to base if the fingers heal skin ulcers. The doctor may also prescribe other vasodilators such as high BP medication, Cozaar, and nitroglycerin cream. Calcium channel blockers help open and relax small blood vessels in the feet and fingers, reducing the severity of RB. Most prescribed drugs include nifedipine and amlodipine (Norvasc), among others.

Sickle Cell Disease

Symptoms of SCD include:

• Sickle cell crises or painful episodes, often severe and can last up to one week.
• High risk of serious infections
• Anemia where RBCs cannot hold adequate oxygen around the body, causing shortness of breath and tiredness.

Diagnostic Tests for SCD

SCD is tested immediately after birth or during pregnancy. Screening is done during pregnancy to check if the baby is at risk of SCD. The blood test is done to check if the mother has sickle cell trait, particularly if the family has a history of SCD.

Treatment for SCD

Individuals with SCD need treatment throughout their lifetime, delivered in specialist SCD centers by a health professional. People with SCD can also use self-care measures, including managing pain and avoiding triggers to control their health. Several treatments of SCD have been proposed, including 1) Keeping warm and taking plenty of fluid to minimize risks of painful episodes; 2) Using painkillers such as ibuprofen; 3) taking daily antibiotics to prevent infections; and 4) blood transfusions in case the symptoms worsen.

Similarities and Differences between RP and SCD

Raynaud’s disease and sickle cell disease share similar features in that they both attack the blood cells and are impacted blood vessels. RP is a rare blood vessel condition, causing the blood vessels in the fingers or toes to constrict, preventing smooth blood flow. This causes the shortage of RBCs in affected parts. Similarly, in SCD, the blood cells (RBCs) become sticky and hard and cannot flow smoothly. The sick cells die faster, leading to a shortage of RBCs (Sundd, Gladwin & Novelli, 2019). Besides, both Raynaud’s disease and sickle cell disease have a degree of hereditary and can be passed from adults to their children. Study shows that Raynaud disease at times runs in families, though the inheritance pattern is unknown. Researchers argue that 30% of individuals with first-degree siblings, parents, or children with primary Raynaud disease have the condition (Mavrogeni et al., 2017). Similarly, sickle cells disease is a genetic blood disorder inherited from birth. It occurs when the child gets two sickle cell genes from the parents.

However, they are different in their causes, both in children and adults. Raynaud’s disease in children and adults occurs due to excessively sensitive blood vessels, toes and fingers, mostly impacted by stress and cold. It happens at any stage in life, childhood and adult (Mavrogeni et al., 2017).  As for sickle disease, it is purely genetic, and people are born with the disease, which they inherit from both parents (Sundd, Gladwin & Novelli, 2019). One cannot get SCD from someone with the condition or develop the disease later in life if it did not occur at birth.