Reynolds syndrome

Overview

Reynolds syndrome is a rare autoimmune connective tissue disorder characterized by the co-occurrence of two primary conditions: primary biliary cholangitis (PBC), a chronic liver disease that affects the bile ducts, and limited cutaneous systemic sclerosis (lcSSc), a subtype of systemic sclerosis that causes skin thickening and vascular abnormalities. The syndrome is named after Dr. Thomas G. Reynolds, who first described it in 1971.

Reynolds syndrome is part of a group of overlapping autoimmune diseases, often referred to as overlap syndromes. It predominantly affects middle-aged women and presents with a combination of symptoms related to both liver dysfunction and systemic sclerosis, such as jaundice, fatigue, skin tightening, and Raynaud's phenomenon. Management typically involves treating both components of the syndrome and addressing symptoms and complications as they arise.

Causes

Reynolds syndrome is an autoimmune disorder, meaning the body’s immune system mistakenly attacks its own tissues. The exact cause is unknown, but genetic predisposition, environmental triggers, and immune dysregulation are thought to contribute to the development of the condition.

Underlying Autoimmune Components:

• Primary Biliary Cholangitis (PBC): A chronic disease in which the immune system attacks the small bile ducts within the liver, leading to cholestasis and progressive liver damage.

• Limited Cutaneous Systemic Sclerosis (lcSSc): A form of scleroderma characterized by thickening of the skin, especially on the face and distal extremities, and involvement of internal organs.

Risk Factors:

• Female gender (predominantly affects women)

• Middle age (typically 40–60 years)

• Family history of autoimmune diseases

• Presence of other autoimmune conditions such as Sjögren's syndrome or lupus

Symptoms

The clinical features of Reynolds syndrome reflect a combination of hepatic and systemic autoimmune involvement. Symptoms vary depending on the severity and progression of the underlying diseases.

Liver-Related Symptoms (PBC Component):

• Fatigue (often profound and chronic)

• Pruritus (itching), especially on the palms and soles

• Jaundice (yellowing of the skin and eyes)

• Right upper quadrant abdominal discomfort

• Dark urine and pale stools

• Hepatomegaly (enlarged liver)

• Progressive liver fibrosis and cirrhosis in advanced stages

Systemic Sclerosis-Related Symptoms (lcSSc Component):

• Raynaud’s phenomenon: Fingers and toes turning white or blue in response to cold or stress

• Skin thickening and tightness: Usually affecting the fingers, hands, and face

• Calcinosis cutis: Calcium deposits under the skin

• Telangiectasia: Dilated small blood vessels on the skin surface

• Dysphagia and reflux: Due to esophageal dysmotility

Other Possible Features:

• Dry eyes and dry mouth (sicca symptoms)

• Joint stiffness or arthralgia

• Pulmonary hypertension (in some cases)

Diagnosis

Diagnosis of Reynolds syndrome involves identifying the presence of both primary biliary cholangitis and limited cutaneous systemic sclerosis through a combination of clinical examination, laboratory testing, and imaging studies.

Laboratory Tests:

• Liver function tests: Elevated alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin

• Antimitochondrial antibodies (AMA): Present in >90% of PBC cases

• Antinuclear antibodies (ANA): Often positive in systemic sclerosis

• Anticentromere antibodies: Common in limited cutaneous systemic sclerosis

• Anti-Scl-70 (topoisomerase I) antibodies: Rare in lcSSc but may be tested to exclude diffuse disease

Imaging and Procedures:

• Abdominal ultrasound or MRCP: To evaluate liver and bile ducts and rule out other hepatobiliary disorders

• Liver biopsy: May be performed to confirm PBC and assess fibrosis if diagnosis is uncertain

• Nailfold capillaroscopy: To detect microvascular changes typical of systemic sclerosis

Treatment

There is no cure for Reynolds syndrome, so treatment focuses on managing symptoms, slowing disease progression, and preventing complications related to both PBC and systemic sclerosis. A multidisciplinary approach is essential, involving hepatologists, rheumatologists, and dermatologists.

1. Management of PBC:

• Ursodeoxycholic acid (UDCA): First-line therapy to slow liver disease progression

• Obeticholic acid: Used in patients who do not respond adequately to UDCA

• Cholestyramine or rifampin for itch relief

• Vitamin supplementation (A, D, E, K) in advanced cases

2. Management of Systemic Sclerosis Features:

• Calcium channel blockers (e.g., nifedipine): For Raynaud’s phenomenon

• PPI therapy: For gastroesophageal reflux

• Immunosuppressants: In selected cases with systemic involvement

• Physical therapy for joint stiffness and skin tightness

3. General Supportive Care:

• Liver transplant in end-stage PBC (rare in Reynolds syndrome)

• Routine monitoring of liver function and autoantibody status

• Regular screening for pulmonary hypertension and osteoporosis

Prognosis

The prognosis of Reynolds syndrome varies depending on the severity and progression of its two main components. With appropriate treatment, many patients can manage symptoms and maintain a reasonable quality of life, though complications may arise over time.

Primary biliary cholangitis, when diagnosed early and treated with UDCA, has a relatively good long-term outcome. However, if untreated or resistant to therapy, it can progress to cirrhosis and liver failure. Limited cutaneous systemic sclerosis is typically less aggressive than the diffuse form, but complications like pulmonary hypertension can still impact survival.

Long-term care includes regular follow-up, symptom management, and monitoring for organ involvement. Early intervention, lifestyle modifications, and coordinated specialist care significantly improve outcomes for individuals with Reynolds syndrome.