Page 779 - Clinical Immunology_ Principles and Practice ( PDFDrive )

750 Part SIX Systemic Immune Diseases

blood away from the skin surface during cold exposure and Digital sympathectomy is used when medical therapy has failed
increases surface blood flow during hot ambient temperatures. to reverse critical digital ischemia. In a few cases, macrovascular
Arteriovenous anastomoses (AVAs) connecting arterioles and occlusive disease (particularly in the ulnar artery) can be surgically
venules allow blood to bypass capillaries, thus allowing rapid and bypassed to improve distal blood flow.
marked increases in cutaneous blood flow. Increased activity of
the sympathetic nervous system via both the CNS (body chilling) Gastrointestinal Involvement
and the peripheral nervous system (local cooling of skin) initiates GI disease is a major cause of morbidity and mortality and
vasoconstriction and heat conservation. Selective responses to accounts for one of the most frequent initial symptoms of
cold by AVAs allow preservation of nutritional blood flow through scleroderma. Every part of the GI tract can be involved, including
skin capillaries. Raynaud phenomenon–associated increase in the oral pharynx, esophagus, stomach, and the small and large
vascular tone results, in part, from a defect in the vascular response bowels. A reduced oral aperture (microstomia) is not only
to normal sympathetic signals. Studies find that α 2 adrenergic cosmetically unpleasant, but it also impairs daily hygiene and
receptors on the smooth muscle cells of cutaneous vessels mediate normal mastication. Periodontal disease is a consequence of
vasoconstriction in AVAs during a response to cold temperature. several factors, including decrease salvia, difficulty in dental care,
This response to sympathetic input is abnormally increased in GI efflux disease, gum recession, and bone resorption. Caries
patients with Raynaud phenomenon. 15 and tooth loss can result. Initial symptoms are difficulty chewing
Raynaud phenomenon is clinically defined as well-demarcated and difficulty swallowing dry or a larger bolus of food.
color changes of the digits induced by cold or emotional stress. Almost all patients with SSc demonstrate evidence of distal
Vascular constriction of AVSs, arterioles, and small arteries in esophageal dysfunction. Clinically, this presents with dysphagia,
the skin and tissues of the digits causes the pallor of the digits, heartburn, and regurgitation typical of gastroesophageal reflux
the phase of complete loss of blood flow. The initial vasospasm disease (GERD). These symptoms are caused by peristaltic dysfunc-
and pallor is followed by cyanosis of the skin caused by venous tion of the distal esophagus, decreased lower esophageal sphincter
pooling and low flow with deoxygenated blood. Finally, after (LES) pressure, and delayed gastric emptying, which is thought
rewarming, the recovery phase occurs with vasodilation manifested to be secondary to autonomic dysfunction. Pathological studies
by hyperemia with blushed reddened skin as blood flow rebounds. of the esophagus show that the smooth muscle (circular greater
Raynaud phenomenon affects as much as 3–5% of the general than longitudinal) of the bowel atrophies without significant
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population. Raynaud phenomenon is considered to be primary fibrosis, vascular injury, or obvious inflammation. Functional
when there is no other associated disease state. In these cases, it and pharmacological studies have shown that a neurogenic
is thought to represent a genetic trait with cold sensitivity as a process precedes smooth muscle dysfunction. Autoantibodies
result of abnormal cutaneous vessel reactivity to environmental directed against enteric neurons and antimuscarinic antibodies
temperatures. In SSc, the disease process targets the peripheral are found, suggesting that an immune process is involved in
vasculature, including AVAs or thermoregulatory blood vessels. the pathogenesis of bowel dysmotility. Esophageal manometric
This leads to not only the abnormal reactivity to ambient evaluation reveals the characteristic triad of low or absent primary
temperatures typical of Raynaud phenomenon but also significant and secondary peristaltic activity in the distal esophagus, normal
structural disease of blood vessels, which causes tissue ischemia proximal esophageal (striated muscle) motility, and the loss of the
as a result of compromise to blood flow within capillaries or LES tone. Complications include reflux esophagitis, esophageal
nutritional vessels. As a consequence of both an exaggerated strictures, mucosal erosions, and bleeding; Barrett metaplasia
response to cold and structural vascular disease, patients with or, very rarely, adenocarcinoma may also develop.
SSc have severe Raynaud phenomenon with multiple, and often Early satiety, bloating, nausea, periodic vomiting, and decreased
prolonged, daily episodes. The severe vascular disease can lead appetite with weight loss are seen secondary to poor gastric
to critical ischemia with digital ulcerations or deep tissue infarc- emptying and retention of food and liquids in the stomach.
tion and gangrene. The vascular disease in SSc is not limited to Gastroparesis is commonly associated with esophageal dysfunction
skin but is systemic. There is evidence that abnormal vascular and aggravates GERD. Dilatation of mucosal capillaries in the
reactivity resulting in tissue injury occurs in the pulmonary, GI tract is common, particularly in the gastric antrum. Gastric
renal, GI, and coronary circulations. antral vascular ectasia (GAVE), also known as “watermelon
Treatment of Raynaud phenomenon must be individualized stomach,” is the major gastric manifestation, which may lead to
and adjusted according to its severity. Initial therapy should occult bleeding and significant anemia. Intestinal dysmotility
include avoidance of cold exposure and use of methods of stress can involve the small and large bowels. Patients may note a
reduction. The best studied medications to treat Raynaud change in bowel habits or present with episodes of pseudoobstruc-
phenomenon are the calcium channel blockers (e.g., nifedipine), tion with severe abdominal pain, bloating, abdominal distension,
which remain the recommended first choice of therapy. Other and vomiting. Persistent diarrhea may be a manifestation of
vasoactive drugs reported to be helpful include the phosphodi- malabsorption of fats as a result of bacterial overgrowth in the
esterase inhibitors, such as sildenafil; serotonin reuptake inhibitors, atonic small bowel and can be associated with dramatic weight
such as fluoxetine; nitrates, such as topical nitroglycerine; and loss and malnutrition. In the late stages, the bowel wall thins
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intravenous prostaglandins. Bosentan, an endothelin-1 receptor out and traps air (pneumatosis cystoides intestinalis). Wide-mouth
inhibitor, was recently shown to reduce the incidence of new diverticuli develop in the colon or the bowel and may rupture.
digital ulcers in patients with SSc but not to alter the frequency Incontinence of stool can occur as a result of dysfunction of
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of Raynaud events. Statins may also protect peripheral blood anal sphincters.
vessels and prevent ischemic digital ulcers, and antioxidants have
the potential to reduce oxidative stress to tissues. Botulinum Pulmonary Involvement
toxin injected locally at the base of the fingers is reported to be Lung disease is now the leading cause of death in patients
helpful, but a controlled clinical trial is needed to define its role. with SSc and accounts for significant lifetime morbidity. Lung