Although judging anyone with their appearance is not very good, external appearance can come really handy when diagnosing some diseases. Identifying a disease early with only mild appearance changes can prevent life-threatening complications in some cases. Let us look into such a disease with appearance changes and also life-threatening complications.
Mrs. Violet, a 45-yer-old housewife, who was reasonably well before, presented to the outpatient department with gradual thickening and tightening of the skin of the dorsum of the hand and difficulty in moving fingers and wrist joints for five months. She also has noticed the same changes over her face for two months, causing difficulty in opening the mouth. She complained about progressive dyspnea and mild dysphagia bothering her for two months as well.
Mrs. Violet admitted that on exposure to cold water, her finger color changes to pale, blue, and red accordingly. She has also complained of pain and swelling of small joints in both her hands for the last two months. The patient had occasional epigastric pain and significant loss of body weight over the past month.
There was no history of fever, skin rash, or abdominal pain, but she had an intermittent dry cough that aggregated at night. Mrs. Violet’s bladder and bowel habits were normal.
She underwent a thorough examination and a few investigations. Considering her clinical features and investigations results, we came to the diagnosis of systemic sclerosis, also known as scleroderma.
Table of Contents
Systemic Sclerosis Essentials
Systemic sclerosis is a connective tissue disorder that causes fibrosis and degenerative changes in the skin, internal organs, and vasculature. Systemic sclerosis is a disease common among females. However, the exact pathogenic mechanisms are yet to be unveiled. There are two types of systemic sclerosis, limited cutaneous systemic sclerosis (LcSSc) and diffuse cutaneous systemic sclerosis (DcSSc).
- LcSSc
Account for 70% of cases. The onset of the disease is with Raynaud’s phenomenon. The skin involvement is limited to the face, hands, forearms, and feet.
- DcSSc
The patient is edematous at onset, followed by rapid skin sclerosis. Raynaud’s phenomenon begins concomitantly or just before edema. Extensive skin thickening involving most of the body can be seen in severe cases.
Systemic sclerosis is a multi-systemic disease in contrast to localized scleroderma syndromes. It involves internal organs and is associated with Raynaud’s phenomenon.
Looking into the pathophysiology of systemic sclerosis, fibroblasts synthesize collagen I and III and other synthetics causing fibrotic changes in the dermis and internal organs. Humoral immunity changes occur with T-lymphocyte activity, complement activation and producing autoantibody against the nuclear antigens. Vascular damage occurs with vessel wall inflammation and intimal proliferation as cytokines cause endothelial damage. This can occur in arteries, arterioles and also capillaries, leading to vasoconstriction and platelet activation.
In Raynaud’s phenomenon, the fingers turn pale, blue and red sequentially with cold exposure and warming up. This is usually associated with a tingling sensation in the fingers. This is caused by spasms of the small blood vessels in the fingers. With time, damages to these small blood vessels can lead to fingertip ulcerations or gangrene. Raynaud’s phenomenon occurs in almost all systemic sclerosis patients of either type.
Patient Presentation in Systemic Sclerosis
How would a patient with systemic sclerosis present to you? They can present with chief complaints like skin thickening and tightness, pain and swelling of joints for months and difficulty in swallowing. Mrs. Violet had many such symptoms in her presentation.
Systemic sclerosis patients can present with other clinical features related to scleroderma. Several clinical features can occur in both LcSSc and DcSSc. Raynaud’s phenomenon, skin thickening and tightness, for example, occur in both.
As the esophagus is affected in most patients with systemic sclerosis, they can present with dysphagia or dyspeptic symptoms like heartburn or regurgitation. Some patients can come with cosmetic issues like changing skin appearance or telangiectasia, small red spots appearing on the face, arm or trunk. Gastrointestinal bleeding can be a complaint in patients with vascular involvement in the esophagus or bowel.
As systemic sclerosis causes internal organ fibrosis, commonly as pulmonary fibrosis, they can present with respiratory symptoms. Systemic sclerosis can be the underlying condition in kidney disease and bowel disease as well.
Crest syndrome, including calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly, and telangiectasia is another presentation of systemic sclerosis. So, you should be clear by now that systemic sclerosis patients can present with a variety of symptoms. We need to have a thorough knowledge and high clinical suspiciousness to identify this disease.
What were our Differential Diagnoses?
Almost all diseases have a variety of presentations. So, when you are seeing a patient, creating a list of possible diseases according to that particular patient’s features is vital.
Considering Mrs. Violet’s presentation, the main worry we had was systemic sclerosis. But we also thought about morphea, which is a localized scleroderma syndrome, diabetic cheirarthritis, nephrogenic systemic fibrosis and eosinophilic fasciitis.
Diabetic cheirarthritis, also known as diabetic stiff hand syndrome, is a condition with thickened skin, diabetic sclerosis, and limited joint mobility of the hands and interphalangeal joints. This is a painless condition in most patients. We can see this condition in patients with long-term uncontrolled diabetes mellitus.
Nephrogenic systemic fibrosis is a systemic fibrotic disease seen in patients with reduced renal function. They usually present with skin lesions in the early stages. It is important to identify this disease early, as this can be fatal.
Eosinophilic fasciitis is a disease caused by inflammation of the tough fibrous tissue bands under the skin. In most patients, fasciitis lesions appear in the arms and legs. Inflammation is caused by the collection of white blood cells, including eosinophils, under the fascia. This condition is also known as Shulman syndrome.
On Examination
In the general examination, Mrs. Violet was looking well but still appeared to be emaciated. Her face was shiny, smooth, tight, and there were hypo-pigmented areas. Forehead wrinkles were lost. Mrs. Violet had a pinched-up and tapered nose giving her a bird beak face. There was puckering of skin around the lips, and she had a small mouth orifice. Multiple telangiectasias were noted in the face and arms.
Mrs. Violet’s hands were smooth, shiny, tight, thick and edematous. The skin of the legs and other parts of the body were normal. She was mildly anemic, but there was no lymphadenopathy, jaundice, clubbing, or koilonychia. Her interphalangeal and metacarpophalangeal joints of both hands were swollen with flexor contractures. There were sclerodactyly and gangrene at the tip of the fingers.
Her pulse rate was 84 beats per minute with a blood pressure of 120/75 mmHg. Mrs. Violet’s respiratory rate was 32 breaths per minute and she had reduced chest expansion with reduced air entry bilaterally. On pulmonary area auscultation, a loud P2 was heard.
We did a thorough examination of all the systems of Mrs. Violet’s. It is a blessing in disguise to find an abnormality early on because we can manage most of the organ dysfunctions successfully if we identify them at early stages.
In our examination, we also have to look for findings that help us exclude our differential diagnoses. There were no signs suggestive of diabetes, and there was no retinopathy. There was no morphea rash over the trunk or abdomen. There was no acrocyanosis suggestive of eosinophilic facilitis.
What Investigations did we Order?
We did a full blood count and the white cell counts were normal. There was no evidence that suggests Mrs. Violet has an infection. But her hemoglobin was 11g/dL and red cell indices were normal. She had a high ESR with normal CRP. These results were suggestive of inflammation. Mrs. Violet’s IgG level was raised.
We ran some specific serology tests on Mrs. Violet and her rheumatoid factor was negative. This is positive only in 30% of patients with systemic sclerosis. But her ANA results were positive. This is positive in about 70% of patients with systemic sclerosis. Anti-topoisomerase-1 and anti-Scl-70 that are suggestive for DcSSC were negative. The anti-centromere antibody, with a speckled nucleolar pattern, is positive 70% in LcSSC and 10% in DcSSC. This was positive in Mrs. Violet.
We did a punched skin biopsy for histopathology. It revealed the presence of calcium deposits under the skin, excessive collagen in thickened skin, and alterations in blood vessels, including vessel wall inflammation, proliferation and endothelial injuries. These are suggestive for scleroderma.
Urine protein was negative, and serum creatinine was in the normal range. So, we could exclude renal involvement of systemic sclerosis. X-ray of the hands revealed deposition of calcium around the fingers, erosion, resorption of phalanges and disorganization of the interphalangeal joints.
Chest X-ray was suggestive of interstitial lung disease and we did a CT scan of the chest for further evaluation. Lung function tests also were suggestive of restrictive lung disease. To diagnose interstitial lung disease, we needed imaging findings and lung function tests.
Reduced diffusing capacity than 50% of its predictive value helped to diagnose pulmonary hypertension. In some cases, the physician may do cardiac catheterization to measure the actual pressure in the pulmonary arteries. As this is an invasive test, we thought it was not necessary for Mrs. Violet. Electrocardiogram was normal, and echocardiogram findings were supportive for pulmonary hypertension.
Barium swallow revealed a reduction of peristalsis, narrowing and dilatation along the pathway. There was no hiatus hernia identified by barium swallow X-ray in Trendelenburg’s position. We did a barium follow-through motility study, which was suggestive for reduced peristalsis movements.
Normal fasting blood sugar level and normal HBA1c helped us to exclude diabetic cheirarthritis. Systemic involvements found in investigations and serology findings were important to exclude localized scleroderma syndrome. Normal renal function tests were not supportive of nephrogenic systemic fibrosis. A biopsy report was the key to excluding eosinophilic fasciitis.
Confirming the Diagnosis
Systemic sclerosis is usually a clinical diagnosis. Considering that Mrs. Violet had most of the typical clinical symptoms such as skin changes, sclerodactyly, Raynaud’s phenomenon, and gastrointestinal tract involvement, we could clinically suspect systemic sclerosis. She also had interstitial lung disease and pulmonary hypertension. Examination findings also were supportive of this.
Investigation findings were important to confirm our diagnosis and to decide on the severity of the disease. Serological investigations, skin biopsy and other investigation results confirmed our diagnosis and excluded other differentials. They were also important to identify the type of systemic sclerosis in our patient. The final diagnosis we came for Mrs. Violet was LcSSc complicated with pulmonary involvement.
How to Manage a Patient with Systemic Sclerosis?
There is no specific therapy for systemic sclerosis. But we can treat symptoms and organ dysfunction. So, the management plan will vary from one patient to another depending on the severity of the disease and patient factors. For Mrs. Violet, we have to make a management plan considering her clinical picture. For now, let us look at how to manage a patient with systemic sclerosis as a whole.
As with any disease, patient education is an important factor. We have to educate the patient about systemic sclerosis and explain that this disease is not contagious or malignant. We have to assess any other comorbidities in the patient and our management plan for systemic sclerosis should go along with the management of those comorbidities.
We should not forget that systemic sclerosis can lead to death with dysfunction of internal organs. So, it is essential to assess their organ function and treat accordingly. Also, we have to consider their view of the disease and try to address cosmetic issues. Some patients may need psychological support too.
Looking into symptomatic management,
- Management of Raynaud’s phenomenon
Exposure to cold should be avoided. We can advise them to use gloves or mittens when working with cold water. Moisturizers should be used to avoid skin dryness. Regular exercise and skin massages will help maintain skin health. Cleanliness of digital ulcers or gangrene is important to avoid infection. They have to avoid drugs such as beta-blockers, oral contraceptives and sympathomimetic drugs.
We can consider antiplatelet according to the extent of vascular involvement. Calcium channel blockers, ACE inhibitors, angiotensin-II receptor blockers may be effective in some patients. If there is no response to the above methods or in severe cases, we can consider prostacyclin analog epoprostenol infusion. If still unresponsive, we will have to consider surgical interventions. If there is an infection on ulcerated skin lesions, we have to give high doses of antibiotics as tissue penetration is poor in scleroderma.
- Arthritis and skin management
Regular exercises and skin moisturizers may limit the progression of contractures.
For pain management, we can use non-steroidal anti-inflammatory drugs. We may have to use alternative analgesics if the patient has dyspeptic symptoms.
- Pulmonary hypertension
For moderate conditions, we can use oral vasodilators, warfarin and oxygen. In advanced cases, we have to consider prostacyclin therapy or oral endothelin receptor antagonists.
- Reflux esophagitis
We can use proton pump inhibitors and prokinetic drugs.
- Myositis or alveolitis
We can use steroids and other cytotoxic drugs.
- Malabsorption
Some patients may need nutritional support with supplements.
Prognosis of Systemic Sclerosis
The prognosis of systemic sclerosis will depend on the type of the disease, age, involvement of organ systems and the extent of the disease.
Bad prognostic factors are having diffuse cutaneous systemic sclerosis, old age, male sex, and involvement of organs such as kidney, lungs and heart. Though our patient, Mrs. Violet, is having LcSSc as she has lung involvement, we have to assess her progression with follow-up.
Follow-up
It is important to keep in touch with the patient as they can involve other systems of the body with time. They can have gastrointestinal and liver involvement at early stages. Respiratory, heart, and kidney involvement is also common among systemic sclerosis patients. Endocrine abnormalities like hypothyroidism and neurological involvement may occur rarely.
We have to evaluate Mrs. Violet every three to six months, depending on her disease progression. There, we have to assess her for other organ involvement. We can modify our management plan according to the progression of the disease and patient preferences.
Summary
Systemic sclerosis is a chronic connective tissue disorder that involves skin, vasculature and internal organs. It has a variety of clinical presentations, but the diagnosis is mainly clinical. We have to identify systemic sclerosis early as it can become life-threatening with organs dysfunction.
References
1.Kumar and Clark’s Clinical Medicine – 9th Edition [Internet] https://www.elsevier.com/books/kumar-and-clarks-clinical-medicine/kumar/978-0-7020-6601-6
2.Davidson’s Principles and Practice of Medicine- 23rd edition(Internet)
3. Scleroderma foundation