Reviewing the challenges of detecting and managing psoriatic arthritis, this author offers key insights on the differential diagnosis of the disease. Drawing upon his clinical experience and a couple of case studies, he also discusses the role of biologic response modifiers within the treatment armamentarium for this condition.

Psoriasis is an inflammatory disease of the skin that affects approximately 1 to 2 percent of the population.1 The average age of onset is 27 and it is usually a lifelong disease with periods of exacerbations and remissions. The etiology of cutaneous psoriasis in unknown but association with HLA-B13, HLA-B17 and HLA-Cw6 genes is common.2

Here one can see psoriasis and psoriatic arthritis on a patient’s hands. Note the silvery violaceous, erythematous plaque type rash on the skin with nail changes of severe psoriasis and onycholysis. The patient also has swelling of the PIP and DIP joints as well as the MCP joints. Here one can see the same patient’s hands after six months of treatment with 15 mg of methotrexate per week and 25 mg of etanercept twice a week. As one can see, there is no rash and minimal scarring from the psoriasis. Even the nail changes have resolved on the hands. There is no swelling of the joints and no sign of arthritis at this time.

Cutaneous psoriasis may have a very significant impact on a patient’s life and livelihood due to infection, economical burden or disability caused by hand, foot or generalized skin involvement.

Psoriasis typically presents as one to many plaques that are deeply erythematous, demarcated, oval and several centimeters in diameter. The plaques usually have a silvery white and scaly surface. They occur commonly on the scalp and over one or more extensor joint surfaces. Intertriginous plaques are present in the axillary, inframammary, umbilical and abdominal folds as well as inguinal, gluteal and popliteal fossae.1 These plaques have little or no scale, are moist and intensely erythematous.

Psoriasis presenting with classic forms of disease will be easy to diagnose. However, some patients may have only one small plaque or a small patchy scale on their scalp. In approximately 30 percent of psoriasis patients, the key to diagnosis will be in their nails.3 Though not pathognomonic, the common change one sees in psoriasis patients is “pitting.” This is icepick-like depressions in the nail plate with onycholysis and separation of the layers of the nail plate and disease of the nail bed.3

Dermatologists typically treat psoriasis and the treatment options include topical steroids, bland keratolytics, topical vitamin D derivatives and a topical vitamin A gel. When it comes to oral steroids, one would only consider these in rare cases due to the fear that dose tapering may trigger erythrodermic or pustular psoriasis.3

How To Differentiate
Between Psoriatic Arthritis
And Other Conditions
There is a crossover between dermatologists and rheumatologists when it comes to the treatment of psoriasis and psoriatic arthritis. Systemic treatment with cyclosporine or weekly methotrexate is for severe cases of psoriasis. With the availability of biologic agents via TNF-a inhibitors such as etanercept (Enbrel, Wyeth), infliximab (Remicade, Centocor) and adalimumab (Humira, Abbott), there have been great additions to the armamentarium for the treatment of psoriasis.

In the above photos, one can see psoriasis plaques, nail changes of onycholysis and swelling of the interphalangeal joints and MCP joints of the right foot.

In our community, rheumatologists have become more comfortable prescribing the biologics so dermatologists began referring patients diagnosed with psoriatic arthritis to the rheumatologists. There are some patients with psoriasis that will develop arthritis in association with their psoriasis. The numbers reportedly range anywhere between 5 to 20 percent.2 Others have postulated that some seronegative rheumatoid arthritis patients are actually psoriatic arthritis patients without plaques. The genes associated most closely with psoriatic arthritis are HLA-Cw6, HLA-Bw36, HLA-DR4 and HLA-DR7.

The diagnosis of psoriatic arthritis can be difficult for several reasons. Some may perceive that a patient has psoriatic arthritis only when he or she has symptoms of both psoriasis and arthritis. However, in adults, skin and joint problems rarely occur at the same time. One may have psoriasis long before arthritic symptoms appear or may have arthritis and not develop psoriasis for decades. For example, it is possible to have joint pain from osteoarthritis with psoriasis and not have psoriatic arthritis.

Here one can see the same patient’s foot after six months of treatment with 15 mg of methotrexate a week and 25 mg of etanercept twice a week. Note the healing of the skin and nail changes with only a small amount of involvement of the great toenail. There is also no swelling of the joints or signs of arthritis.

Psoriatic arthritis may also mimic other conditions, making the diagnosis of the disease even more complicated. Accordingly, clinicians should consider conditions such as rheumatoid arthritis, gout and Reiter’s syndrome among other conditions when working through the differential diagnosis.

Rheumatoid arthritis is one of the most debilitating forms of arthritis. It occurs when an autoimmune response causes inflammation in the lining of the joints, especially those in the hands and feet. If this disease is left untreated, the inflammation over time leads to joint destruction and permanent pain and disability.
Gout is a type of arthritis that is characterized by sudden, severe attacks of pain, redness and tenderness in a single joint, usually in the joint at the base of the great toe. Unlike rheumatoid arthritis, gout is not an autoimmune disorder. Instead, an excess of uric acid levels in the blood can cause gout. This is caused by a natural process of the breakdown of purines in the body. If a patient lacks an enzyme to process the uric acid, it builds up in the serum and precipitates out as crystals into a joint.

Reiter’s syndrome is a form of reactive arthritis that causes inflammation in the joints, eyes, genitals and urinary or digestive tract. Often, a bacterial infection triggers Reiter’s syndrome in people who have a genetic tendency to develop the disease.

Key Insights
On Diagnostic Testing
While there is no single test to confirm the diagnosis of psoriatic arthritis, clinicians can utilize key diagnostic tests to help differentiate psoriatic arthritis from other conditions.

Radiographs can help pinpoint changes in the joints that are supportive of the diagnosis of psoriatic arthritis. These include erosive changes and new bone growth in the distal joints, “pencil in cup” erosions, lysis of terminal phalanges, periostitis and new bone growth at sites of enthesitis.4

Joint fluid tests are helpful. One may obtain cultures to look for a septic arthritis and crystal analysis can be helpful in detecting gout or pseudo-gout.

Testing for rheumatoid factor would help rule out rheumatoid arthritis. If the test is positive for RA, the patient probably does not have psoriatic arthritis.

What You Should
Know About NSAIDs
Some clinicians employ NSAIDs, both COX-1 and COX-2 inhibitors, to control the pain, swelling and morning stiffness that may occur with psoriatic arthritis. However, keep in mind that all NSAIDs can irritate the stomach and may cause ulcers and gastrointestinal (GI) bleeding. Other potential side effects include renal damage, fluid retention and heart failure. In general, NSAIDs are not particularly beneficial for psoriatic arthritis and some may even make skin problems worse. However, some clinicians still use them for people with minor joint pain and psoriatic arthritis.

The COX–2 inhibitors are a class of drugs that are supposed to be less irritating to the stomach yet still suppress cyclooxigenase (COX), the enzyme causing inflammation. Traditional NSAIDs, such as aspirin, suppress COX-1 and COX-2. The COX-1 enzyme helps protect the stomach lining while the COX-2 enzyme is involved in inflammation. Celecoxib (Celebrex, Pfizer) and other “COX-2” inhibitors are specific for COX 2 and are theoretically safer for the stomach but can still cause hypertension and edema.

When NSAIDs are not effective in controlling pain or inflammation, or are not appropriate for certain patients, one should consider other modalities such as disease modifying antirheumatic drugs (DMARDs) or biologic response modifiers.

What About DMARDs?
Disease modifying antirheumatic drugs are a class of medications that help limit joint damage and reduce the pain and inflammation of psoriatic arthritis and rheumatoid arthritis. The most commonly utilized drugs in this class are sulfasalazine, methotrexate and azothiaprine.

All of these medications will have the same side effects and potential risks when one uses them for psoriatic arthritis as with other rheumatic diseases. Accordingly, clinicians need to monitor these in the same fashion. Due to the slow initial onset of action of these drugs, one may not notice any effects from the medications for several weeks. Clinicians will often place the patient on some modest dose of steroids, which will have a rapid onset along with the initial DMARD. Once the DMARD has begun to provide relief, clinicians will then taper the steroid dose slowly.

Assessing The Impact Of Biologic Response Modifiers
Biologic response modifiers represent the latest class of medications clinicians have employed for psoriatic arthritis. These medications block an immune system protein called tumor necrosis factor-alpha (TNF-a). Researchers have found elevated concentrations of TNF-a in the joints of patients with psoriatic arthritis. In the past, researchers have found similar elevations in the joints of those with rheumatoid arthritis.4

Here is a pre-treatment picture of psoriatic plaques and an erythematous rash on a patient’s back.

Treatment of psoriatic arthritis and psoriasis with etanercept, infliximab or adalimumab is generally well tolerated and significantly improves symptoms. Clinicians may utilize etanercept or adalimumab as monotherapy or in combination with methotrexate. One would generally prescribe infliximab in combination with methotrexate in order to prevent the formation of human anti-chimeric antibodies (HACA).

These medications have become a mainstay of treatment for psoriatic arthritis and psoriasis. The results are extremely dramatic. In my clinical experience, the skin disease, joint pain, swelling and morning stiffness of patients improves, usually within one to two weeks of initiating treatment with the TNF-alpha blockers.

Side effects of TNF-alpha blockers include abdominal pain, dizziness, headache and respiratory problems. A more serious, even fatal side effect is the risk of infections, especially in people whose immune systems are already compromised.

Here is a view of the same patient’s back after six months of treatment with 15 mg of methotrexate a week and 25 mg of etanercept twice a week. Note the healing of the skin with only some residual scarring.

In these cases, one needs to caution patients to be vigilant for elevated temperatures or any signs or symptoms of an infection, and to report these signs to their provider. All of these medications have been associated with the risk of resurgence of latent tuberculosis.

Also bear in mind that whenever you consider TNF-alpha blockers for a patient, he or she must have an intermediate strength purified protein derivative (PPD) test prior to beginning the medication and the current recommendation is a yearly PPD while on the drug.

Case Study: When A Patient Fails To Respond To Treatment Of Seronegative RA
The patient is a married, 24-year-old female, who presents with a chronic illness that she has had for approximately two years. She has a diagnosis of seronegative rheumatoid arthritis but has not responded well to NSAIDs, sulfasalazine or methotrexate (only 10 mg/week).

She was very ill, weighed only 84 pounds and she had an iron deficient anemia with a Hgb of 6.9 and Hct of 23. She had flexion contractions of bilateral knees of 20 degrees, synovitis of 34 joints and tenderness of 26 joints. Our first impression was she had been under-treated for sero-negative RA. However, we then discovered a few very small patches of silvery, scaly rash on her scalp and she gave us a history of minor psoriasis for several years before the arthritis began.

We then changed our diagnosis to psoriatic arthritis. We began treating her anemia with iron supplements and increased her methotrexate to 15 mg/ week. We also started her on the TNF-alpha blocker adalimumab at 40 mg SC q for two weeks. We also referred her to an orthopedic surgeon for arthroscopic debridement of some scar tissue that was blocking full extension of her knee joints. Her initial CRP was 76 (normal < 5).

Within one month of initiating this therapy, the patient’s Hgb improved to 9.1 with a Hct of 27.4 and a CRP of 14.4. She had undergone the arthroscopic surgery for her knees and was in physical therapy for ROM exercises, and only lacked about 4 degrees of full extension. She had mild synovitis in 12 joints and tenderness in 8 joints. Her weight improved to 89 pounds and she generally felt well.

In a subsequent follow-up visit two months later (after three months of methotrexate 15 mg/week and adalimumab 40 mg SC q for two weeks), the patient’s Hgb was 13.5 with an Hct of 31.7 and a CRP of 2.8. She had full range of motion in her knees with no synovitis or tenderness. The patient had no swollen or tender joints on joint count. Her weight had improved to 102 pounds and she said she felt better than she had in four years since her first child was born.

The patient remained on the same therapy for three years and seven months with no side effects until December, 2005. At that time, she lost insurance coverage due to a divorce. She had been stretching out her medicines since that time to try to get by. She had some prednisone and the adalimumab but no methotrexate. The patient had been taking about two to three mg of prednisone every two to three days and 40 mg of adalimumab every six to eight weeks when her symptoms would become almost unbearable.

Recently, she presented to the office because she was completely out of all of her medications. She had an outbreak of psoriasis on the palmar region of her hands and soles of her feet. She also had a flare of her arthritis with 12 tender and eight swollen joints on joint count and her CRP was 28 again.
We are currently attempting to help her qualify for some patient assistance for her medicines.

As one can see from this case, the TNF-alpha blockers seem to be very effective agents in treating psoriatic arthritis and psoriasis.

Case Study: How The Combination Of Methotrexate And Etanercept Relieved A Psoriasis Outbreak
A 57-year-old male has a long history of psoriasis of the skin but presented with an extreme outbreak of the condition in May 2002. He also had psoriatic arthritis of multiple joints and onycholysis of all nail plates as well.

He had previously worked 10 hours a day, five days a week as a bread truck driver. When he had the outbreak, the patient could no longer walk, drive or even button his shirt or pants because of the swelling and pain in his hands and feet. The arthritis was the worst in the distal interphalangeal joints but was also present in the ankles, knees, wrists and elbows. The psoriasis caused secondary infections of the skin and nails and the patient became completely disabled in a matter of weeks from his disease.


When we first examined the patient, his dermatologist had been trying to treat his psoriasis with vitamin D preparations and topical medications but the patient was not improving.

As expected, the patient’s initial labs were seronegative. We did test for HIV and it came back negative. His initial CRP was 26 (normal <0.7) and he did have a mild anemia with a Hgb of 13.4 and a Hct of 41.1. The patient was miserable with painful swollen joints and the joint count was not done on the initial visit.
We started the patient on methotrexate and tapered the dosage up to 15 mg/week and initiated etanercept 25 mg SC every Tuesday and Friday.

Note the psoriasis plaques on this patient’s forearm. In the photo (on the right), one can the clearing of the forearm with some scarring after six months of treatment with 15 mg of methotrexate per week and 25 mg of etanercept twice a week.

We had the patient return in one month for lab work. His skin and joints were vastly improved at this time. The patient had much less swelling, his psoriasis was subsiding and even his nails were beginning to improve. His lab work was better with a CRP of 4.8, a Hgb of 13.7 and a Hct of 42.6. However, the patient stated he did not feel all that much better yet and was still fatigued most of the time.

The patient then returned at four months after initiating treatment. His psoriasis had all but disappeared. His arthritis was “cured” according to the patient and he asked if he could stop taking the medications. Even his nails, which were so terrible on presentation, had fallen off and were growing back rapidly in a normal fashion. His anemia had resolved and his CRP was normal at <0.7.

We convinced him that the medications would help prevent him from having another flare of this disease and he has agreed to stay on the treatment regimen. He has aged some over the years and is now eligible for Medicare. We have had to switch the TNF-alpha blocker due to insurance coverage changes but the patient has continued to do well. His lab numbers have continued to remain normal over the years and he has not experienced any flares of skin or arthritis disease.

In Conclusion
As these cases point out, the TNF-alpha blockers are instrumental in treating psoriasis and psoriatic arthritis. Based upon my clinical experience using these medications, I believe that patients with this disease who do not respond rapidly to topicals or DMARDs for psoriasis — and certainly if they have arthritis related to psoriasis — should be treated with TNF-alpha blockers.