Systemic Sclerosis Sine Scleroderma - Causes, Symptoms, and Management

Introduction

Systemic sclerosis is a generalized autoimmune multisystem disease. It affects organs such as the skin, lungs, stomach, heart, and kidneys. Systemic sclerosis is also called scleroderma (SSc). The main types of scleroderma are localized and diffuse.

What Is the Cause of Scleroderma?

The exact cause of the condition is not clear. However, environmental and genetic factors play a role in its pathogenesis. Infectious agents such as Epstein Barr virus (EBV), Cytomegalovirus (CMV), and Parvovirus B19 are implicated. The relationship between human leukocyte antigen (HLA) and SSc is also known.

What Is Sine Scleroderma?

Sine scleroderma is a very rare subtype of systemic sclerosis. It is also known as systemic sclerosis sine scleroderma (ssSSc). The skin manifestations of the usual SSc are either totally or partially absent. First defined in 1962 by Rodnan and Fennel, it is also sometimes denoted as ‘visceral scleroderma.’ The exact prevalence of ssSSc is difficult to determine. The rare features of this disorder make its diagnosis usually late. Still, there is a rough estimate of five percent of patients suffering from ssSSc. These contain isolated cases of reported ssSSc.

What Are the Types of Systemic Sclerosis Sine Scleroderma?

Based on clinical signs, the following are the categories of ssSSc.

1. ssSSc Type I: Complete Visceral Scleroderma: Skin involvement is not present. Internal organs are affected. Raynaud’s phenomenon is present in this category (it is a vascular abnormality that usually manifests on the fingers or toes).

2. ssSSc Type II: Incomplete Visceral Scleroderma: The usual organ involvement is evident. The typical skin thickening present in the other types of SSc is absent. However, features involving the skin, such as pitting scars and calcium deposits, are appreciated.

3. ssSSc Type III: Delayed Cutaneous Involvement: Along with organ involvement, skin features can be present but are detected later during the disease. It is imperative to analyze the order of symptom appearance in a patient to distinguish this form from the diffuse SSc.

What Are the Signs and Symptoms of Systemic Sclerosis Sine Scleroderma?

ssSSc affects females more than males. It is mostly seen in middle-aged people. The clinical presentation of ssSSc is similar to that of SSc, but organ involvement is more. The gastrointestinal and pulmonary symptoms are most commonly presented.

1. Gastrointestinal: Symptoms include swallowing difficulties, abdominal cramps, constipation, bloating, nausea, and vomiting. Heartburn due to gastroesophageal reflux disease (GERD) is common. Inflammation of the esophagus (esophagitis), strictures, and bleeding are complications of esophageal dysmotility.

2. Pulmonary: Shortness of breath (dyspnoea), mostly at exertion, is found among patients. Other symptoms are dry cough and fatigue. Pulmonary artery hypertension (PAH) and interstitial lung disease (ILD) are also frequent. Less common incidences are pulmonary hemorrhage, pneumonia, and obstructive airway disease. Progressive PAH, if untreated, can lead to death.

3. Cardiac: Cardiac involvement is slightly less reported. Arrhythmias, chronic heart failure, heart block, increased heart rates, and pericardial effusions are noted. The cardiac association is found to be of poor prognosis.

4. Renal: Less frequently, the kidneys are affected in ssSSc patients. Scleroderma renal crisis (SRC) and chronic renal failure have been reported. Acute severe hypertension and accumulation of nitrogen bodies characterize scleroderma renal crisis. The nephritic syndrome has been described to occur more in women.

5. Others: Autoimmune disorders are known to be associated. These are Hashimoto’s thyroiditis, Grave’s disease, Sjogren’s syndrome, and rheumatoid arthritis. Also, dry mouth can be seen due to saliva reduction, which increases the incidence of dental decay.

How Is Systemic Sclerosis Sine Scleroderma Diagnosed?

A complete history and physical examination are essential to establish the timeline of symptoms. In addition, regular blood pressure monitoring is required. The diagnosis of ssSSc is based on the criteria given by Poormoghim et al. They proposed the absence of skin involvement, positive anti-nuclear antibody (ANA), Raynaud’s phenomenon, absence of any other connective tissue disease, and visceral organ involvement.

What Are the Investigations Done in Systemic Sclerosis Sine Scleroderma?

Following are the investigations.

1. Capillaroscopy: It is done for Raynaud’s phenomenon. A nail fold capillary examination is performed. The doctor views the nail fold under a microscope. Abnormally enlarged capillaries and micro-bleeding sites represent a positive nail fold capillary exam.

2. Direct Immunofluorescence: This test determines the anti-nuclear antibody (ANA). It is positive in 90 % of the cases.

3. Laboratory Investigations: Renal function tests, urine protein measurements, and urine microscopy are important. Inflammatory marker evaluation can rule out arthritis. A complete blood count can exclude anemia.

4. Gastrointestinal: For esophageal dysmotility, endoscopy, barium swallow, and pH probing are useful. Besides, a CT scan is conclusive of esophageal dysmotility in imaging excess air in the esophagus.

5. Pulmonary: Chest X-ray and high-resolution computed tomography scan (HRCT) are useful in detecting ILD. Moreover, pulmonary function tests are done, namely, lung spirometry, lung volume assessment, and diffusion capacity. In the case of PAH, transthoracic echocardiography (TTE) is advised.

6. Cardiac: ECG and Holter analysis is done for arrhythmias. Pericardial effusions are seen on TTE. Magnetic resonance imaging (MRI) is convenient if the heart muscles are involved.

How Is Systemic Sclerosis Sine Scleroderma Managed?

The treatment of ssSSc depends upon the disease severity and state. However, various therapeutic agents explained below can slow the disease progression.

• For Raynaud’s phenomenon, calcium channel blockers such as Nifedipine and Amlodipine have proven to be very beneficial. Other medications include Pentoxifylline, Nitroglycerine, Iiloprost, Sildenafil, Tadalafil, Bosentan, and Ambrisentan. All the above-written medications act as vasodilators. In addition, Botulinum toxin has been reported to be effective in some cases.

• Omeprazole and Pantoprazole are proton pump inhibitors (PPIs) that are effective in heartburn. For dysmotility, prokinetic agents are encouraged. Lifestyle modifications such as avoiding spicy foods, large and late meals, and eating small meals are recommended. For dry mouth, sugar-free gums and lozenges are used. Artificial saliva and frequent drinking water are advised.

• A multidisciplinary team is required to manage ILD. Immunosuppressive agents used include Cyclophosphamide, Mycophenolate Mofetil, and Azathioprine. Cyclophosphamide is used for initiation and azathioprine for maintenance therapy. Further, Nintedanib, a tyrosine-kinase inhibitor, and Tocilizumab, a monoclonal antibody, have recently been approved by FDA. All these medications improve dyspnoea and lung fibrosis. Stem cell transplantation is still under trial. PAH is managed by vasodilators.

• Calcium channel blockers are beneficial in heart dysfunction and increasing blood supply. Also, anti-arrhythmic agents and, sometimes, pacemaker installation are advocated for arrhythmias.

• Angiotensin-converting enzyme inhibitors (ACEi) are the only successful medications against SRC. SRC is a serious condition requiring emergency treatment. Captopril has a short half-life and is preferred. Dialysis should accompany the medication to treat chronic renal failure.

• Pain-relieving medications for joint inflammation are given. Arthritis is managed with Hydroxychloroquine and Methotrexate. Physiotherapy to improve muscle function is advised. Azathioprine is also useful for chronic muscle inflammation.

Corticosteroids precipitate SRC, and beta-blockers can trigger Raynaud’s phenomenon. Hence, patients should avoid using them.

Conclusion:

ssSSc is an irreversible disease. However, treatment is aimed at reducing symptoms to a large extent. Patient education regarding the signs and symptoms should be a primary requisite. Close patient monitoring and regular follow-ups are critical in improving the standard of living. Overall, the prognosis is good as the survival rates have improved over the years, and many patients live normal healthy life due to increased awareness.