bubble_chart Overview

Psoriasis nature of disease Arthritis (psoriasis arthritsi, PA), also known as arthropathic psoriasis, is an inflammatory joint disease associated with psoriasis. The disease has a prolonged course, is prone to recurrence, and in the advanced stage can lead to joint ankylosis, resulting in disability. Psoriasis is more common among arthritis patients, occurring 2–3 times more frequently than in the general population, while arthritis is also prevalent among psoriasis patients. In a 10-year survey, Leczinsky found that the incidence of arthritis among psoriasis patients was 6.8%, significantly higher than that in non-psoriasis populations. Women are more susceptible than men. According to Nobol's report, PA accounts for approximately 1% of psoriasis patients [5]. Since this disease, along with Reiter's syndrome and ankylosing spondylitis, is associated with HLA-B27 and presents with negative rheumatoid factor, while sharing similar clinical manifestations, it is classified as a seronegative spondyloarthropathy.

bubble_chart Etiology

The exact mechanism remains incompletely understood. The occurrence of this disease is related to complex interactions among genetics, immunity, environment, and infection.

1. Genetics: In the pathogenesis of psoriatic arthritis, genetic factors play a significant role and demonstrate polygenic inheritance. Early familial studies suggested an increased prevalence of PA in families with a proband suffering from psoriasis. In one study, 11 out of 88 probands developed PA. Recent findings indicate that histocompatibility antigens HLA-A₁, B₁₆, B₁₇, B₂₇, B₃₉, Cw₆, and D₇ are associated with psoriatic arthritis, with approximately half of patients carrying HLA-B₂₇

. In contrast, the histocompatibility antigens for psoriasis alone are HLA-B₁₃, B₁₇, Cw₆, and DR₇. McHugh found that HLA-DR7 is associated with chronic severe peripheral arthropathy, while HLA-B₂₇ is significantly correlated with spondylitis or axial involvement, as well as juvenile psoriatic arthritis affecting the sacroiliac joints.

2. Immune Abnormalities:

⑴ Existing evidence suggests that immune mechanisms play a crucial role in the pathogenesis of psoriasis. Dual-labeling immunofluorescence tests using HLA-DR antibodies and monoclonal antibody OKT₆ demonstrated that HLA-DR⁺ keratinocytes are present in psoriatic skin lesions and synovial cells but not in normal-appearing skin or Langerhans cells. The expression of HLA-DR correlates with disease activity. Patients with HLA-DR⁺ keratinocytes have a higher incidence of psoriatic arthritis. Therefore, immunochemical staining to detect HLA-DR⁺ keratinocytes in psoriatic lesions may help predict the high risk of arthritis in psoriasis patients. HLA-DR₄ is associated with bone erosion in arthritis.

⑵ Viral or bacterial infections can induce immune abnormalities: Recent studies have shown that the incidence of psoriasis is higher in populations infected with the human immunodeficiency virus (HIV) compared to the general population. Arthritis can occur at any stage of HIV infection and is often severe. HIV has been isolated from joint fluid and confirmed in monocytes and lymphocytes.

In psoriatic plaques, there is an accumulation of Gram-positive bacteria and elevated anti-streptococcal antibodies. In both psoriasis and psoriatic arthritis patients, lymphocyte transformation in synovial fluid shows an enhanced response to streptococci.

These findings suggest the involvement of immune interactions and immune factors in psoriasis and arthropathy. DR⁺ keratinocytes, Langerhans cells, or similar cells may process bacterial or other antigens and interact with dermal T cells, leading to disease onset. However, this does not prove that immune abnormalities are the primary cause of psoriatic arthritis.

3. Environmental Factors Cold, dampness, seasonal changes, mental stress, depression, endocrine disorders, trauma, etc., have been identified as significant environmental triggers for PA in genetically predisposed individuals. Cases of acro-osteolysis following local trauma have been reported. Some suggest that the mechanism by which joint injury induces arthritis is similar to the Koebner phenomenon observed in psoriatic skin.

bubble_chart Pathological Changes

Synovial membrane tissue biopsy shows grade I hyperplasia and hypertrophy of synovial cells in the early stage of the lesion, accompanied by a small amount of fibrinoid exudation. There is grade I edema and fibrous tissue proliferation beneath the synovial cells, with obvious proliferation and congestion of small blood vessels, along with a small amount of lymphocyte and plasma cell infiltration. In the advanced stage of the lesion, fibrous tissue in the synovial membrane significantly increases, with residual small blood vessels showing thickening and luminal narrowing.

bubble_chart Clinical Manifestations

Psoriatic arthritis (PA) typically has an insidious onset. The pain is usually milder than that of rheumatoid arthritis, though occasionally it may present acutely like a gout attack. The disease predominantly manifests between the ages of 30 and 40, and is less common in children under 13. Joint symptoms may worsen or improve in tandem with skin symptoms; joint manifestations may also appear after repeated exacerbations of psoriasis, or they may coincide with pustular or erythrodermic psoriasis. Gladman analyzed 220 cases of PA and found that 68% of patients initially had psoriasis, with arthritis developing after an average of 12.8 years; 15% developed both psoriasis and arthritis within a year; and 17% presented with arthritis first, followed by psoriasis after an average of 7.4 years.

1. Joint Manifestations Moll et al. and Andrews classified the disease into five clinical types based on the nature of psoriatic joint involvement:

⑴ Oligoarticular Type: The most common, accounting for about 70%. It involves one or a few finger or toe joints asymmetrically, accompanied by joint swelling and tenosynovitis, giving the digits a "sausage-like" appearance.

⑵ Rheumatoid Arthritis-like Type: Accounts for 15%, presenting as symmetric, polyarticular arthritis with claw-like deformities. Patients may exhibit clinical features resembling rheumatoid arthritis, including morning stiffness, symmetric involvement, fusiform swelling of proximal interphalangeal joints, and ulnar deviation in advanced stages. Occasionally, rheumatoid nodules or positive rheumatoid factor may be present. Some consider these cases an overlap between rheumatoid arthritis and psoriasis.

⑶ Asymmetric Distal Interphalangeal Joint Type: Accounts for 5%, primarily affecting the distal interphalangeal joints. Symptoms include redness, swelling, and deformity, often starting in the toes before spreading to other joints. Unlike rheumatoid arthritis, there is no ulnar deviation, pain is milder, and nail dystrophy is common. This type is more prevalent in males.

⑷ Arthritis Mutilans Type: Accounts for 5%, representing a severe, destructive form. It often affects multiple joints in the hands, feet, and sacroiliac joints. Characterized by progressive periarticular erosion leading to osteolysis, with or without bony ankylosis, resembling neuropathic arthropathy but painless. Skin psoriasis in this type is typically extensive and severe, often pustular or erythrodermic.

⑸ Ankylosing Spondylitis-like Type: Accounts for 5%, presenting as isolated spondylitis or overlapping spondylitis and peripheral arthritis. Spinal lesions feature non-marginal syndesmophytes, particularly in the thoracic and lumbar regions, with narrowing and sclerosis of facet joints, erosions at disc margins, and anterior vertebral osteophytes, mainly in the lower cervical spine. Peripheral arthritis affects distal interphalangeal joints, showing bilateral symmetric or unilateral asymmetric erosive arthritis. Inflammation may extend beyond the synovium into tendon insertion sites. Some patients may have sacroiliac joint involvement. A hallmark of this type is spinal stiffness, particularly after inactivity and in the morning, lasting over 30 minutes.

2. Nail Changes Approximately 80% of PA patients exhibit nail abnormalities, which can provide early diagnostic clues. Since the nail bed and phalanges share a blood supply, chronic psoriatic nail damage leads to vascular changes that eventually affect the underlying joints. The severity of bone changes correlates closely with nail pathology, often occurring in the same digit. Common nail changes include pitting, transverse grooves, longitudinal ridges, discoloration, subungual hyperkeratosis, and onycholysis.

3. Skin Manifestations Skin lesions typically occur on the scalp and extensor surfaces of the limbs, especially the elbows and knees, appearing as scattered or generalized patches. Lesions present as papules or plaques, round or irregular, covered with thick silvery-white scales. Removing the scales reveals a shiny membrane (the "film sign"), and scraping this membrane produces pinpoint bleeding (Auspitz sign). These three features are diagnostically significant.

4. Other manifestations In psoriatic arthritis, damage to other systems may also occur. Common manifestations include: acute anterior uveitis, conjunctivitis, scleritis, and keratoconjunctivitis sicca; inflammatory bowel disease and gastrointestinal amyloidosis; spondylitic heart disease, characterized by aortic valve insufficiency, persistent conduction block, and unexplained cardiac hypertrophy. Systemic symptoms such as fever, weight loss, and anemia may also occur.

bubble_chart Auxiliary Examination

There is no specific diagnostic test for this disease. Non-specific changes include an increased erythrocyte sedimentation rate, grade I anemia, and elevated γ and α₂ globulins. Approximately 10–20% of patients exhibit grade I hyperuricemia. Rheumatoid factor is negative. Lupus cells, antinuclear antibodies, and other autoantibodies are also negative. Synovial fluid analysis is non-specific, with a white blood cell count ranging from 2–15×10⁹/L, predominantly neutrophils. Occasionally, in cases of significant effusion, the white blood cell count may reach 100×10⁹/L. Synovial fluid viscosity is reduced.

This disease resembles rheumatoid arthritis, often affecting the distal interphalangeal joints, sacroiliac joints, and spine. Common radiographic findings include cartilage loss; articular surface erosion; joint space narrowing; destructive arthritis showing marked osteolysis and ankylosis, possibly presenting with the "pencil-in-cup" deformity; isolated marginal or non-marginal ligamentous osteophytes; villous periostitis; osteoporosis; and cystic changes in bone tissue.

bubble_chart Diagnosis

Patients with psoriatic skin lesions are easy to diagnose. If joint symptoms appear first, without skin lesions or with atypical lesions, diagnosis becomes difficult.

bubble_chart Treatment Measures

There are currently many treatment methods for this disease, but most can only achieve short-term clinical effects and cannot prevent recurrence.

1. General treatment: Patients should rest appropriately, reduce labor intensity, and avoid excessive fatigue and joint injury. All joints should be adequately exercised daily to maintain and improve joint function.

2. Non-hormonal anti-inflammatory drugs: These drugs have strong anti-inflammatory effects and are highly effective in relieving inflammatory pain. Commonly used drugs include enteric-coated aspirin, indomethacin, piroxicam, aminosugar indomethacin, ketoprofen, and fenbid. Recently, there have been reports that indomethacin may worsen psoriasis skin lesions, so its use remains controversial.

3. Anti-tumor treatment: Although these drugs have certain therapeutic effects, they have toxic reactions and are prone to relapse after discontinuation. Therefore, they are not the direction for psoriasis treatment, and strict selection of indications is required during application. Liver and kidney function and white blood cell counts should be checked regularly before and during medication. Effective drugs for psoriatic arthritis include:

⑴ Methotrexate (MTX): MTX mainly acts on the DNA synthesis phase (S phase) of the cell cycle. After 36 hours of administration, all psoriatic epidermal cells are inhibited.

There are differing opinions on the administration method. Some use a single dose orally, intramuscularly, or intravenously, with a weekly dose of 25–50mg; others take 2.5mg orally daily for 5 days, rest for 2 days, then take another 5 days, followed by a 7-day rest. Weinstein proposed the principle of epidermal cell kinetics, suggesting oral administration of 2.5–7.5mg every 12 hours, totaling 3 doses within 6 hours, followed by the same method weekly.

⑵ Razoxane (ICRF159): This drug mainly acts on the advanced stage of the pre-mitotic phase (G₂) and the early stage of mitosis (M). Its efficacy for psoriatic arthritis may be better than MTX. Patients with pre-existing liver disease should not use MTX, or if liver perianal abscess-like reactions occur after medication, this drug should be discontinued. Atherton et al. reported that this drug can rapidly suppress associated arthritis. The main side effect is neutropenia, which can occur rapidly, sometimes severely, and may even be fatal.

Usage: The initial dose is 125mg, three times daily, for 2 days a week. After 4–8 weeks, the dose may be appropriately increased based on white blood cell counts, to 125mg or 250mg, three times daily, for 2 days a week, used alternately. For psoriatic arthritis, it can also be administered for 3 days a week.

⑶ Lymphocyte inhibitors: Cyclosporine A can inhibit T lymphocytes, mainly T_H cells, reducing HLA-DR antigen expression.

Dose and method: Generally, 5–12mg/kg daily, administered orally. The plasma concentration should typically not be lower than 100ng/ml, with the most effective range above 200ng/ml. However, concentrations above 400ng/ml may cause kidney perianal abscess-like reactions, and exceeding 600ng/ml may lead to neurological toxicity. This drug should not be used with ketoconazole or melphalan to avoid high plasma concentrations and severe side effects.

⑷ Heavy metal preparations: Comparative studies show that heavy metal agents have a higher remission effect on psoriatic arthritis but are ineffective for psoriatic skin lesions.

Commonly used is sodium arsenite, also known as cacodylate sodium. Administered intramuscularly at 100mg daily, for 10–20 days per course.

⑸ Anti-malarial drugs: Chloroquine phosphate has variable efficacy for psoriasis. Some reports suggest better effects for photosensitive and psoriatic arthritis, while others report it may induce psoriasis and erythroderma during treatment. It is rarely used now.

6. Corticosteroid hormones: Currently, this type of medication is generally not recommended for the treatment of PA. It is sometimes used only for patients with severe conditions who do not respond to other treatments.

4.Chinese medicine Chinese medicinals   Chinese medicine believes that the nature of psoriasis arthritis is mostly caused by wind-dampness obstruction and liver-kidney deficiency.

⑴ Wind-dampness obstruction: Mainly manifests as joint swelling and pain, with a relatively short disease course.

Treatment principle: Eliminate dampness and clear heat, invigorating blood to remove toxin.

Formula: Modified Pubescent Angelica and Taxillus Decoction. Herbs used: Gentian, Saposhnikovia Root, mulberry twig, Pubescent Angelica, Chinese Clematis Root, Dictamnus dasycarpus, Glabrous Greenbrier, Chinese Angelica, Red Peony Root, suberect spatholobus stem, Achyranthes Root.

For predominant upper limb symptoms, add Turmeric and kadsura pepper stem; for predominant lower limb symptoms, add fourstamen stephania root.

⑵ Liver-kidney deficiency: Mainly manifests as joint deformity and limited mobility, with a longer disease course.

Treatment principle: Modified Jianbu Hidden Tiger Pill. Herbs used: Prepared Rehmannia Root, Cornus officinalis, Chinese Angelica, Moutan Bark, Eucommia Bark, Dipsacus, Floweringqince Fruit, Cibot Rhizome, Tortoise Carapace, tiger bone, Black-Tail Snake, Glabrous Greenbrier, Siegesbeckia herb, Lycopodium clavatum, etc.

⑶ Chinese patent drug: ① Tripterygium wilfordii tablets: Contains ethyl acetate extract of Tripterygium wilfordii, including triptolide, which has strong anti-inflammatory and immunosuppressive effects. Take 2 tablets each time, 3 times daily. Alternatively, Tripterygium wilfordii glycosides tablets can be used at 1–1.5 mg/kg per day, divided into 3 doses. ② Kunming Mountain Begonia tablets: Each tablet contains 0.5 mg of ethanol extract powder of Kunming Mountain Begonia (equivalent to 2 g of raw herb). Take 3–6 tablets each time, 3 times daily. Single dose should not exceed 18 tablets.

5. Topical medications   Mainly targeting psoriatic skin lesions. Commonly used drugs include: 5% Sulfur, 5–10% salicylic acid, 2–10% coal tar, 0.1–1% anthralin, 1:10,000–1:20,000 india mustard seed gas, 0.05% nitrogen mustard, 10–15% camptothecin, 2–5% chrysarobin, 0.025%–0.1% vitamin A acid, etc., formulated as ointment, solution, or tincture.

6. Physical therapy

⑴ Photochemotherapy: Also known as Psoralea plus long-wave ultraviolet therapy. This therapy is effective for peripheral-type psoriasis arthritis but ineffective for axial arthritis.

Treatment method: Oral administration of 8-methoxypsoralen (8-MOP) 0.6 mg/kg, followed by UVA irradiation after 2 hours. Use a dose slightly below the minimal erythema dose, 2–3 times per week. The treatment course should not be too long, and the total cumulative dose should not exceed 500–600 J/cm².

⑵ Extracorporeal photochemotherapy: Recently reported by Wilfer to be effective for psoriasis arthritis. After treatment, improvements were observed in ESR, pain, duration of morning stiffness, grip strength, and joint swelling to varying degrees.

7. Local joint treatment

⑴ Intra-articular, bursal, or tendon sheath injection of long-acting corticosteroids: Shows some efficacy. However, repeated injections may easily cause infection.

⑵ Surgical treatment: For patients with joint deformity and functional impairment, arthroplasty can be performed to restore joint function. Currently, hip and knee repair surgeries have been successful. However, joint stiffness after surgery remains an unresolved issue, which is more prominent in psoriasis arthritis than in rheumatoid arthritis.

bubble_chart Differentiation

1. Rheumatoid arthritis is a migratory polyarthritis that predominantly affects the small joints of the extremities with symmetrical involvement. In the advanced stage, the metacarpophalangeal joints deviate ulnarly. Rheumatoid nodules may be observed on the skin. Rheumatoid factor is positive.

2. Reiter's syndrome typically presents with nonspecific urethritis, conjunctivitis, arthritis (especially in weight-bearing joints of the lower limbs), and skin lesions. Patients with this syndrome may exhibit keratoderma blennorrhagicum, and the joint symptoms closely resemble those of psoriatic arthritis. Diagnosis of atypical cases requires follow-up over a period of time.

3. Ankylosing spondylitis predominantly affects males under 30 years of age. Early symptoms include lumbago, discomfort in the lumbosacral region, intermittent or alternating sciatica, and stiffness in the lower limbs and lower back. In the advanced stage, the spine and lower limbs develop a rigid, arched deformity. Radiographic findings reveal a "bamboo spine" appearance.

4. Gout-induced acute arthritis has a sudden onset, often occurring at night and improving during the day. After repeated attacks over months to years, it progresses to chronic gout, leading to joint deformities and stiffness. Diagnosis is aided by clinical symptoms, hyperuricemia, the presence of gouty tophi, the detection of urate crystals in synovial fluid, and a positive response to treatment with colchicine or allopurinol. {|103|}