- How does rheumatoid arthritis affect the skin?
- How to Maintain Healthy Skin With Rheumatoid Arthritis
- What Are Rheumatoid Arthritis Nodules?
- Rheumatoid Arthritis and Skin Vasculitis
- RA Medication Side Effects and Skin
- Risks for Bruises and Sunburns Increase with Some Medication
- Sticking With Your Medication May Be the Most Important Skin-Protection Step
- What is Adult onset Still’s Disease (AOSD)?
- Symptoms of Adult Onset Still’s Disease
- Diagnosing the condition
- Further reading
- Rheumatoid arthritis
- What is rheumatoid arthritis?
- General cutaneous manifestations
- Specific cutaneous manifestations
- Rheumatoid vasculitis
- Fever, Rash, and Swelling: Don’t Miss This Diagnosis
How does rheumatoid arthritis affect the skin?
RA is associated with several different skin conditions. A person may experience none, one, or multiple skin conditions due to their RA. These include the following:
Nodules are hard lumps that form directly under the skin. They range from about the size of a pea to that of a golf ball. They may develop over bony or fleshy areas of a person’s body.
Nodules are not usually painful but may be treated directly to reduce their size. In rare cases, surgery may be required to remove the nodule, especially if the nodule is infected.
RA medications may be the cause of rashes on a person’s skin. These rashes are believed to be allergic reactions to the medications.
Medications that may cause a rash include:
If a person experiences a rash as a side effect of medication they are taking, they should tell their doctor. Depending on the severity of the reaction, the doctor may change the dose or the medication itself to a different one.
It is important not to suddenly discontinue or reduce a medication without speaking to a doctor.
A doctor may also prescribe an antihistamine to combat or reduce the reaction, or even steroids for severe reactions.
Medications that are used for the treatment of RA can also make a person more susceptible to other skin problems. For example, some of the drugs cause a person to bruise more easily or be more sensitive to sunlight.
Some people with RA experience chronic or recurring hives that develop on the skin. Hives are similar to a medication rash, but they may form independently of a medication. Allergists now recognize chronic, unexplained hives as a symptom of RA.
Livedo reticularis is a skin condition that is only occasionally associated with RA. However, some research suggests that serious underlying conditions can cause livedo reticularis.
Livedo reticularis is often considered a benign rash that occurs or becomes more evident during colder weather. The condition is caused by spasms in blood vessels that produce a net-like pattern of purplish lines.
Livedo reticularis can cause other complications, including:
- painful nodules
The condition can also indicate the presence of a peripheral vascular disease or a clot in the blood vessels.
How to Maintain Healthy Skin With Rheumatoid Arthritis
Rheumatoid arthritis, an inflammatory condition affecting 1.5 million Americans, is mostly characterized by painful, stiff, and swollen joints. But rheumatoid arthritis can inflict damage far beyond the joints. In fact, the chronic disease can wreak havoc throughout the whole body.
“With rheumatoid arthritis, something in the body goes haywire and it starts attacking itself,” says Mahsa Tehrani, MD, rheumatologist and co-founder of the Arthritis & Rheumatology Clinical Center of Northern Virginia in Vienna. “Though it is mostly within the joints, really any organ system can, unfortunately, be affected.”
One such organ system is the skin. There are several common skin conditions that people living with rheumatoid arthritis have, either as a direct result of the disease or from the medication used to treat it. Below are some of these conditions, along with tips to maintain healthy, beautiful skin despite having RA.
What Are Rheumatoid Arthritis Nodules?
Many people living with RA develop rheumatoid arthritis nodules, or small lumps beneath the skin. Nodules often appear near a joint at the elbow, knuckles, or fingers, though they can be anywhere on the body. They are more common in more severe forms of the disease, or if it has been left untreated for a while.
Usually these nodules are painless, but depending on their location, they can cause some discomfort. “If the nodules are on the surfaces of the arms, like the elbow or wrist, usually they don’t bother people except aesthetically,” says Robert Keenan, MD, MPH, assistant professor of medicine in the division of rheumatology and immunology at Duke University School of Medicine in Durham, North Carolina. “But if they’re at a place where pressure is applied, like the bottom of the foot, for example, then it can be painful,” he adds.
Rheumatoid arthritis nodules vary in size and can be as small as a pea or as large as a golf ball. Usually, once the disease is treated with medication, the nodules will disappear.
Rheumatoid Arthritis and Skin Vasculitis
Rheumatoid arthritis can also cause inflammation of the blood vessels, known as vasculitis. Most often, small blood vessels are involved, notably those that supply blood to the skin on the fingertips. “This usually looks like a blue or purplish rash near the fingernails,” Dr. Tehrani says.
More serious forms of vasculitis can occur in larger blood vessels, such as those in the legs, and cause painful rashes or ulcers. If left untreated, these ulcers can become infected, so see a doctor immediately if you suspect an issue.
RA Medication Side Effects and Skin
Certain medication used to treat RA can have negative side effects on the skin, as well. Nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) are commonly prescribed to ease painful symptoms of the disease, but can sometimes cause skin rashes. This can be a sign of an allergic reaction to the medication, so speak to your doctor if your skin breaks out after starting a new drug.
Pain at the injection site and skin rashes also occur in less than 30 percent of people who use biologic response modifiers, or biologics — genetically engineered proteins derived from human genes — to treat RA symptoms. Biologics are injected beneath the skin, so itching, burning, and discoloration can occur at the injection site. Usually these side effects will go away on their own, but Dr. Keenan warns, “if the reactions get larger with each injection, definitely contact your doctor.”
Risks for Bruises and Sunburns Increase with Some Medication
Certain RA medication may make bruising of the skin more likely to occur, either by thinning the skin or interfering with blood clotting. Another common side effect of RA medication is an increased sensitivity to sunlight. When taking these drugs, it’s important to practice sun safety rules, including avoiding direct sunlight, especially between the hours of 10 a.m. and 2 p.m.
If you have any concerns over medication side effects, speak to your doctor. He may prescribe a lower dose or switch your medication entirely, depending on the severity. But don’t despair if you experience minor irritation when you begin a new drug. “Some medications can take from two weeks to up to three or four months to work properly,” Tehrani says, “so just because something isn’t 100 percent working for you immediately, don’t give up.”
Sticking With Your Medication May Be the Most Important Skin-Protection Step
The most important way to maintain healthy skin while living with RA, Tehrani says, is to follow a doctor-prescribed medication schedule. “If a patient is complying with the medication their rheumatologist gives them and they’re taking it on time, they usually won’t have to deal with many of these side effects,” she says.
Sun protection is also key to avoiding skin complications. “Wear long sleeves and hats to protect yourself when you go outside,” Tehrani says, “and always wear sunscreen.” Keenan also recommends seeing a dermatologist yearly for a skin check.
Finally, good lifestyle habits can go a long way to ensure healthy, beautiful skin. “Weight management, a healthy diet, and trying to reduce stress have tremendous benefits with any chronic condition,” Tehrani says. “The better you take care of yourself, the less likely it is that flare-ups will occur.”
What is Adult onset Still’s Disease (AOSD)?
Adult Onset Still’s Disease (AOSD) is an auto-inflammatory disease. This means that the inflammation is generated by a disturbance in immune function. The immune system generates inflammation, without the usual stimulus to inflammation, such as infection or injury. The condition affects the joints and internal organs. It is usually present before the age of 40 years. Women are slightly more commonly affected than men. There are no known risk factors and there is usually no family history. Occasionally a virus may trigger the illness; however a sore throat is also a symptom of the illness and therefore there may be confusion over whether this is the cause or the start of the illness.
Symptoms of Adult Onset Still’s Disease
The main features of this condition are fever, joint pains and rash. It is not uncommon though for the arthritis to not be present at the start of the illness. The patient may simply be very unwell with very high levels of inflammation in their blood and no other cause found. It is for this reason that patients with AOSD often present to the ‘infectious diseases’ department. The fever comes on quickly, usually once a day in the afternoon or evening and then spontaneously resolves, often going below normal. The temperature may be associated with flushing. The rash, which often but not always accompanies the fever is a salmon pink, blotchy, non-itchy rash. It can, however mimic many other rashes and on occasion may be itchy and appear like raised lumps. It is often on the upper arms, abdomen and thighs. When the patient has a fever they feel very miserable, with a headache, severe muscle pain and often a very sore throat. Serositis, which is inflammation of the lining of the lungs (pleura), lining of the heart (pericardium) and lining of the abdominal cavity (peritoneum) may occur. This would account for severe chest pain, particularly when taking in a deep breath. The lymph nodes, which are swollen and tender, are often widespread. This may suggest the possibility of a lymphoma (cancer of the lymph nodes). Biopsy of the lymph nodes shows only reactive changes and no evidence of cancer. Other diagnoses which need to be excluded include rare infections and inflammatory bowel disease. If the joint symptoms present early then it is less likely there will be a diagnostic delay.
Diagnosing the condition
Blood tests such as ESR and CRP confirm a high level of inflammation. Other rheumatoid arthritis tests such as rheumatoid factor and anti-CCP antibody, as well as the other auto-antibodies are all negative. Very often the full blood count will show a high white blood cell count and platelet count but there will be anaemia (low haemoglobin). This is because the high level of inflammation suppresses the manufacture of red blood cells and the utilization of iron in the marrow. In contrast, the ferritin, which is the iron storage protein, will be very high and this is often used as a diagnostic test. X-rays of the joints in the early stage are very unlikely to show any abnormality. Although joint swelling can be seen on x-ray, ultrasound would be more useful as a test to visualise inflammation of the joints. A chest x-ray may show an enlarged heart due to inflammation of the heart lining and because there may be fluid around the heart, which can also appear in the lung cavity. The spleen, which is essentially a big lymph node, can be enlarged.
Once the diagnosis has been made, treatment needs to be commenced in order to relieve symptoms and suppress inflammation. This is important because it helps the patient to feel better but also so that damage to the joints can be prevented. It is very difficult in the early stages to predict the course of the illness. A third of patients will have a mono-phasic illness. This means that the illness lasts a few months and then fades away with treatment and does not recur. A third of individuals will have a relapsing course with intermittent flare ups over subsequent years. These flare ups are often less severe than the first episode. A further third of individuals, however, will have a disease course which lasts a long time. They will require major immuno-suppressant drug therapy for control and there may be some effect on major organs. The joints that are involved are similar to those affected in rheumatoid arthritis, and once the fevers and rashes have settled it may be difficult to differentiate the rheumatoid “hand” from an AOSD disease “hand”. The wrists are predominately involved as well as the small joints. Occasionally early damage to a large joint such as the hip may occur. This may in part be due to the very high doses of steroids that were used to control the inflammation at the start of the illness (as steroids can cause osteoporosis if used in high doses/for long periods of time).
There is much research underway to understand the mechanism behind the auto-inflammatory disease and what generates the inflammation. It is known that high levels of the inflammatory proteins interleukin-1 and interleukin-6 are present. The biological agents (monoclonal antibodies to these proteins) such as anakinra and tocilizumab are consequently used increasingly for the treatment of this condition.
Early treatment is aimed at controlling the symptoms of fever and arthritis with anti-inflammatory drugs such as ibuprofen, naproxen and even high dose aspirin. These may be prescribed before the definitive diagnosis has been made. Painkillers such as paracetamol, codeine and tramadol may also be helpful. Corticosteroids such as prednisolone are very often used to control inflammation and fever and to improve anaemia. The anaemia that occurs is not responsive to iron supplementation. When steroids are used they will often be given with other drugs to help to prevent side-effects. These might include protection against stomach ulcers (omeprazole or lansoprazole) and bone protection to prevent osteoporosis (alendronate and calcium). The aim is to use as low a dose of steroid as possible to control the inflammation but in the early stages it is often high doses, often intravenously, that are required.
Due to the long-term impact that steroids can have on the body, the disease will also need steroid-sparing medication for control. Methotrexate which is the most commonly used disease modifying drug in rheumatoid arthritis is also used in AOSD. Ciclosporine is also sometimes used to prevent and treat a rare complication of AOSD called macrophage activation syndrome (MAS). This rare complication is associated with a precipitous drop in blood count and can potentially be very serious. Biological therapies that are often used include the anti-TNF agents infliximab and adalimumab and also, tocilizumab and anakinra. Methotrexate is used together with these agents in order to prevent the development of antibodies against these drugs. Once disease control has been achieved the drugs will be reduced very cautiously. It is usually not possible to predict outlook until at least 1 year after onset of disease.
For some of these drugs, monitoring, in the form of regular blood tests may be required to check for potential side-effects.
Once disease is controlled and the individual feels well again, there is no reason why they should not be able to work and function extremely well in everyday life. The steroids may have caused some side effects such as weight gain and mood change, but this will reduce and disappear as the steroid dose is tailored down.
As with all chronic illness, and particularly this disease, which has such an impact when it hits, frustration and low mood may occur and much understanding, support and encouragement will be needed for the patient and their family. Low self-esteem and self-consciousness is not unusual when individuals have put on weight due to the steroids, missed work or education and feel excluded from life. It takes time to “recalibrate” and this is important to recognise. The transition from being a healthy individual to being one who needs to take tablets, attend hospital appointments and have life-adjustments needs to be taken into account.
NRAS article on osteoporosis
NRAS article on Disease Modifying Anti-Rheumatic Drugs (DMARDs)
NRAS booklet on biologic drugs
Still’s disease causes
References available on request
What is rheumatoid arthritis?
Rheumatoid arthritis (RA) is classified as a connective tissue disease. It is a chronic systemic inflammatory disorder that damages the joints of the body. Classic symptoms of rheumatoid arthritis include joint swelling, deformity, pain, weakness, and stiffness of the smaller joints such as those of the hands, wrists, elbows, knees, ankles and feet. These are referred to as the articular manifestations of the disease. When rheumatoid arthritis affects other organs of the body these are known as extra-articular manifestations.
Skin changes of rheumatoid arthritis are considered extra-articular manifestations and can be divided into two types: general cutaneous manifestations and specific cutaneous manifestations.
General cutaneous manifestations
Patients with rheumatoid arthritis may experience a wide array of non-specific skin changes. General signs and symptoms include:
- Skin becomes atrophic (thin and wrinkled), making it fragile and easy to bruise
- Skin on the back of the hands may become pale or even translucent
- Nails may become brittle and split length-wise
- The palms become reddened (palmar erythema)
Nonspecific signs of rheumatoid arthritis
Specific cutaneous manifestations
Many people with rheumatoid arthritis form subcutaneous nodules. These are lumps that appear on or near the affected joint and are visible just beneath the skin.
- Occur in about 25% of patients
- Most common extra-articular feature of RA
- Found in 75% of patients with RA-associated Felty syndrome (in which there are reduced numbers of neutrophils in the blood and the patient has a large spleen)
- More common in men than women
- Generally develop later in the RA disease process but can occur before any joint disease
- Skin coloured, singular or multiple, and range in size from millimetres to centimetres in diameter
- Most are firm and painless but ones on the soles of the feet or palms may feel uncomfortable
- Most commonly occur on those areas prone to mild, repetitive irritation, e.g. fingers, heel, forearms, back
- Rheumatoid nodules have characteristic pathology, but it may sometimes be confused histologically with granuloma annulare.
- Although nodules are mostly benign, complications such as infection, ulceration, and gangrene can occur following breakdown of skin overlying the nodules
- Usually no treatment is necessary unless nodules become debilitating, ulcerated, or infected. Surgical removal may be performed.
- Methotrexate-induced accelerated nodulosis usually occurs as small nodules on fingers, elbows and other joints
- Rheumatoid nodulosis is a relatively benign rheumatoid variant
Neutrophils are a type of white blood cell (leucocyte). They are present in bacterial infections. They are the prominent cell seen on skin biopsy of some uncommon inflammatory skin diseases known as neutrophilic dermatoses.
Sweet disease and pyoderma gangrenosum are other neutrophilic disorders sometimes seen in association with rheumatoid arthritis.
Rheumatoid neutrophilic dermatitis
Interstitial granulomatous dermatitis
Also known as ‘rheumatoid papules’, interstitial granulomatous dermatitis presents as skin coloured or red papules or plaques often on the trunk. Annular configuration is often noted. Interstitial granulomatous dermatitis is rare. The diagnosis is made when distinctive pathological features are seen on biopsy.
Interstitial granulomatous dermatitis
Cutaneous vasculitis may be a complication of rheumatoid arthritis and is characterised by dark purplish areas on the skin (purpura) caused by bleeding into the skin from blood vessels damaged by rheumatoid arthritis. Skin changes caused by rheumatoid vasculitis include:
- Skin ulcers (usually leg ulcers) may be extensive and painful
- Petechiae (purplish spots) or purpura
- Nail fold or edge breakdown (digital infarcts)
In addition to skin changes, rheumatoid vasculitis can cause many internal symptoms, including sensory or motor neuropathy (loss of sensation), hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), bowel ulcers, and haematuria (blood in urine).
Fever, Rash, and Swelling: Don’t Miss This Diagnosis
The Differential Diagnosis
This presentation fits within a diagnostic territory of an autoimmune disorder, a systemic inflammatory disorder, malignancy, and an infection. Let’s further examine the differential diagnosis.
Supporting this diagnosis are the patient’s fever, leukocytosis, high ESR and CRP, and adenopathy. When symmetric polyarthritis, rash, liver function test abnormalities, and hepatosplenomegaly are also present, the following need to be considered:
Bacterial endocarditis: The absence of a murmur and subacute bacterial endocarditis splinter hemorrhages argues against endocarditis, as does the presence of symmetric polyarthritis. Negative blood cultures would rule this out.
Hepatitis B and C: Both hepatitis B and C can be associated with polyarthritis, abnormal liver test results, rash, adenopathy, spleen and liver abnormalities, and anemia, but one would expect higher levels of AST and ALT in someone this sick. In addition, the leukocytosis would be uncommon. Hepatitis B and C serologic testing would help to rule out these conditions.
Disseminated gonococcemia: The patient’s fever, joint inflammation, skin rash, leukocytosis, and elevated ESR would support this diagnosis, but the adenopathy, hepatosplenomegaly, symmetric polyarthritis, and transient nature of the skin rash would be uncommon. In addition, joint inflammation is usually migratory or monoarticular, while skin lesions are usually pustular or papular. Blood, genital, rectal, and throat cultures can support this diagnosis; synovial fluid cultures could be negative even in the face of gonococcal arthritis.
Septicemia: The patient’s symmetric polyarthritis would be highly uncommon in the setting of a staphylococcal, streptococcal, or gram-negative septicemia, in which monoarticular or oligoarticular joint inflammation would be more likely. Blood cultures would be diagnostic.
Rheumatic fever: The absence of a sore throat, migratory polyarthritis, and carditis would argue against this diagnosis. Throat culture and antistreptolysin-O test would be diagnostic if rheumatic fever was present.
Lyme disease: Symmetric polyarthritis, hepatosplenomegaly, adenopathy, transient rash, and this degree of leukocytosis would be uncommon in Lyme disease.
Parvovirus B19: The patient’s rheumatoid arthritis-like symmetric polyarthritis is characteristic of parvovirus B19 infection; however, the hepatosplenomegaly, adenopathy, and leukocytosis would be uncommon in this disorder.
Supporting a diagnosis of malignancy are the patient’s fever, adenopathy, hepatosplenomegaly, leukocytosis, elevated ESR and CRP, and abnormal liver function test results. However, the symmetric polyarthritis argues against this diagnosis. A breakdown of malignancies to be included in the differential diagnosis follows:
Leukemia: The presence of symmetric polyarthritis would be uncommon in leukemia, in which joint problems are often present in a single joint and mostly occur at night. In addition, the leukocytosis and thrombocytosis would be unexpected in leukemia. A normal differential count and peripheral smear would rule against this.
Lymphoma: Symmetric polyarthritis, leukocytosis, and thrombocytosis would be uncommon in lymphoma.
Multiple myeloma: Multiple myeloma usually presents with back pain, elevated ESR, and anemia. The patient’s degree of fever, hepatosplenomegaly, adenopathy, and rash would be uncommon in this condition.
Solid tumors, such as colon cancer, renal cell cancer, breast cancer, or lung cancer, do not usually present with symmetric polyarthritis, this degree of fever, or rash.
Autoimmune, Systemic Inflammatory Disorder
Any and all of this patient’s clinical features should arouse consideration of the following disorders:
Systemic lupus erythematosus: All of this patient’s clinical manifestations could be seen in a patient with lupus except for leukocytosis and thrombocytosis, which would be highly uncommon. In addition, hepatomegaly along with splenomegaly is not often seen. Results of an antinuclear antibody test would be positive in someone with lupus and this level of inflammation.
Rheumatoid arthritis (RA): Symmetric polyarthritis is classic for RA, but fever, hepatosplenomegaly, adenopathy, and rash would rule strongly against it. Results of a rheumatoid factor and anti-cyclic citrullinated peptide test can be negative early in the course of RA. However, this patient’s presentation is not that of RA; RA is not a febrile disease.
Ankylosing spondylitis: Ankylosing spondylitis usually presents with back pain and morning stiffness. If peripheral arthritis exists, it is usually in the shoulders or hips and is never symmetric.
Reactive arthritis: The joint pain present in reactive arthritis is not generally symmetric. Rather, it is usually asymmetric and associated with large joints and lower extremities; in addition, it is often associated with low back pain and stiffness and sacroiliac joint inflammation. There is often a history of recent dysentery or urethritis. The patient’s degree of fever and leukocytosis are not characteristic of reactive arthritis, and hepatosplenomegaly and adenopathy are unheard of in this condition.
Ulcerative colitis and Crohn’s disease: There is usually a history of one of these disorders, and any associated joint inflammation is generally asymmetrical and involves lower extremities. Lower back pain and stiffness, as well as sacroiliitis, are often seen. This patient’s degree of hepatosplenomegaly and adenopathy would be uncommon.
Psoriatic arthritis: Most patients with psoriatic arthritis have a history of psoriasis. In addition, this patient’s systemic presentation would be uncommon. Joint inflammation can be RA-like in psoriatic arthritis, but it is usually asymmetric and is seen in the distal interphalangeal and lower-extremity joints.
Adult-onset Still’s disease: This patient demonstrates the characteristic presentation of Still’s disease, or systemic-onset juvenile RA. Ultimately, however, this is a “rule-out” diagnosis — one that is made after blood tests, cultures, and imaging studies have found no sign of infection or malignancy. Supporting data would be an elevated serum ferritin level.
Polyarteritis nodosa: This is a predominantly male disorder that presents with fever, skin lesions, neuropathy/mononeuritis multiplex, joint and muscle inflammation, and renal disease. Anemia, leukocytosis, and thrombocytosis are common. Suggesting against polyarteritis nodosa is the presence of adenopathy and hepatosplenomegaly. The diagnosis would be supported by tissue biopsy of skin, muscle, or nerve.
Wegener’s granulomatosis: The triad of sinus inflammation, lung nodules, and nephritis is characteristic in Wegener’s granulomatosis, and RA-like polyarthritis can be present. However, adenopathy and hepatosplenomegaly would be uncommon. The diagnosis is supported by the very common finding of a positive result on a serum anti-neutrophil cytoplasmic antibody test (ANCA) and a tissue lung biopsy showing necrotizing granulomatous vasculitis.
Churg-Strauss vasculitis: Asthma, eosinophilia, and pulmonary infiltrates are characteristic of Churg-Strauss vasculitis, and patients often present with neuropathy, skin lesions, joint inflammation, and renal disease. A positive finding on a perinuclear ANCA test is found in 50% of patients. Hepatosplenomegaly and adenopathy are not common in this condition.