Connective Tissue Disease And Overlap Syndromes
The connective tissue diseases are a family of closely related disorders. They include: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE or lupus), polymyositis-dermatomyositis (PM-DM), systemic sclerosis (SSc or scleroderma), Sjogren’s syndrome (SS) and various forms of vasculitis.
These diseases have a number of common features:
Although lupus most often occurs alone, many people with lupus also have symptoms characteristic of one or more of the other connective tissue diseases. In this circumstance, a physician may use the term “overlap” to describe the illness. There are several well-recognized overlaps that may affect people with lupus.
Lupus and Rheumatoid Arthritis
In lupus, joint pain (arthralgia) is common. Joint swelling (arthritis) may be present in some cases, but the majority of those with lupus experience joint pain without swelling or only intermittent swelling. In rheumatoid arthritis (RA), joint swelling is always present and pain is common but less prominent. Because rheumatoid arthritis is more likely than lupus to cause joint deformities and bone destruction, joint replacement or reconstructive surgery is more often required in RA than in SLE. If a person with lupus develops severe arthritis with joint deformities, he/she should be considered to have rheumatoid-like arthritis. In some instances, the physician might have reason to believe that both diseases — SLE and RA — have occurred in the same person. When arthritis develops in the course of lupus, treatment with non-steroidal anti-inflammatory drugs (NSAIDs), low doses of cortisone, and the antimalarial drug hydroxychloroquine (Plaquenil) are usually helpful. People with lupus who have typical rheumatoid arthritis are prescribed the standard forms of RA treatment. These include methotrexate, sulfasalazine and in some cases, more potent drugs to suppress joint inflammation.
Many persons with lupus have muscle pain (myalgia), but a few have muscle weakness due to inflammation (myositis). The “muscle weakness” that people with lupus report is most commonly due to fatigue or high doses of cortisone. In polymyositis-dermatomyositis, the primary problem is muscle weakness due to muscle inflammation. In myositis, weakness especially affects the hips (inability to rise from a chair or toilet seat, or to climb stairs unassisted) and shoulders (inability to lift a weight onto a high shelf or comb one’s hair). Typically, there is little or no pain associated with the weakness. People with myositis have increased blood levels of creatine kinase (CK, a substance that leaks from injured muscle), abnormal electrical activity of muscles (seen in an electromyogram, or EMG), and muscle cell degeneration and inflammation that is found in a muscle biopsy. Prednisone or other cortisone-like drugs are most often recommended for the treatment of myositis, and may be used in combination with other immune-suppressing drugs. Cortisone itself, in high doses, may actually cause muscle weakness of the hips and shoulders, very similar to what occurs in myositis. But in this condition, called “steroid myopathy,” the CK, EMG, and the muscle biopsy do not suggest inflammation, and recovery of strength promptly follows reduction of the cortisone dose.
Lupus and Scleroderma
The hallmark of scleroderma (SSc) is thickened skin (sclero=hard, derma=skin) which affects the fingers, and often the hands, forearms, feet, and face. If skin thickening is widespread, it may extend to the upper arms, thighs, chest, and abdomen. These changes are due to the excessive production and uncontrolled laydown of collagen, the substance normally present in scar tissue. The variety of skin rashes seen in lupus are due to inflammation, rather than fibrosis. These include the facial “butterfly” rash and photosensitivity reaction (rash, hives or blisters immediately after exposure to sunlight or other sources of ultraviolet light). The latter is limited to the skin surfaces exposed. An exception is discoid lupus, which consists of spots or patches of rash, mostly in sun exposed areas (face, ears, extremities), which typically cause scarring and skin pigment changes. The appearance of scleroderma and discoid lupus are entirely different, and should be easily distinguished from one another by your physician.
Other features less common in SLE than in SSc include: scarring of the lower portions of the lung (pulmonary fibrosis); difficulty in swallowing solid foods such as bread or meat; and heartburn or indigestion from stomach acid “refluxing” (coming back up) into the esophagus. Difficulty swallowing and reflux are due to sluggish and uncoordinated motion of the muscle layer of the esophagus (esophageal dysmotility). Scleroderma often leads to finger and hand deformities as well, due to the combination of skin thickening, arthritis, tendinitis and tenosynovitis (inflammation and scarring of tendons and their lining tissues). These processes ultimately result in limited movement of the fingers. Raynaud’s phenomenon — when fingers turn blue or white with cold — occurs in 95 percent of people with scleroderma and in 40 percent of persons with lupus.
The primary treatment approaches to SSc are quite different from those for lupus. Therefore, treatment for scleroderma-like problems in people with lupus should be individualized and directed at the particular problems present at any given time.
Mixed Connective Tissue Disease
Some individuals have symptoms and signs of three connective tissue diseases, i.e., lupus, polymyositis-dermatomyositis, and scleroderma. At any given time, the combination of problems encountered by the patient may vary considerably, from no active disease to features of one, two, or all three of these conditions at the same time. These persons often (but not always) have one specific blood antibody in their blood (anti-U1RNP antibody) but not the other antibodies commonly associated with SLE, SSc, or PM-DM. Whether this is an entirely separate disease, or a situation in which one person has three diseases, remains uncertain. However, the presence of a single blood antibody is a strong point in favor of a distinctive disease. As in the other circumstances mentioned above, treatment should be individualized and directed at the particular problems present at any given time.
Henrik Sjögren was a Swedish ophthalmologist and the first to recognize that dry eyes and dry mouth were often found in people with connective tissue diseases. These symptoms are caused by the accumulation of immune system cells (lymphocytes) in and around tear and saliva producing glands. The build-up of cells disturbs the function of these glands and leads to reduced production of tears and saliva. This condition also interferes with the protective mechanisms of the eye and mouth. Eye inflammation and ulcers of the cornea, as well as fungal infections of the mouth (thrush), occur with increased frequency in those with Sjogren’s. Rarely, a person with this disorder develops a malignancy (cancer) affecting the lymphocytes (lymphoma). Today, Sjogren’s syndrome is itself accorded the status of a distinct connective tissue disorder.
Sjogren’s Syndrome also occurs in some people with lupus. They have an increased frequency of sun-sensitive rashes and Sjogren’s-related blood antibodies (anti-SSA and anti-SSB antibodies). Women with anti-SSA antibodies are at increased risk of having babies with “neonatal lupus.” Symptoms in the infant can be as minor as a temporary lupus-like skin rash, or as serious as permanent damage to the electrical system of the heart which results in a very slow heart rate (complete heart block).
The best treatments for Sjogren’s Syndrome include: artificial tears (usually satisfactory) and either artificial saliva (most often unsatisfactory) or a saliva stimulant such as pilocarpine, and hydroxychloroquine (Plaquenil). Eye drops containing cyclosporin have also just been introduced and have significant benefit for dry eyes in some cases. Arthritis, fatigue and skin rash in people with Sjogren’s is often treated with Plaquenil.
Frequency Of Overlap Syndromes In People With Lupus
The majority of people with lupus have lupus alone. Between 5 and 30 percent of people with lupus report having overlap symptoms. The likelihood of a person with lupus also having an overlap disease is 15 percent, distributed as follows:
Heredity And Overlap
It is unusual (less than 10 percent of the time) for a person with lupus to have a close family member (parent, child, brother, or sister) who also suffers from lupus. However, it is common for persons with lupus to have relatives (including grandparents, aunts/uncles, cousins) with other connective tissue diseases such as rheumatoid arthritis, Sjogren’s Syndrome, scleroderma, etc. These co-occurrences raise the possibility that heredity may be a factor in all of the connective tissue diseases. Most scientists agree that important hereditary associations with these diseases are present in some families. Additional research is needed to shed light on this important question.
Prognosis For People With Lupus And Overlap Syndromes
It is important for those with lupus to be aware of the symptoms that might indicate the development of “overlap” features, since these symptoms and abnormalities may be best managed with treatments not typically used for lupus. Fortunately, when an overlap syndrome is present, the symptoms characteristic of the other connective tissue diseases involved are usually mild and not life-threatening.