Raynaud’s phenomenon associated with psoriatic arthritis

Abstract

We report a case of Raynaud’s phenomenon in a patient with psoriatic arthritis (PsA). A middle-aged right-handed housewife presented with complaints of severely painful hand discolouration for 1 week, which usually worsened with cold exposure. She was diagnosed with PsA 6 months earlier. Her PsA was well controlled with weekly methotrexate. Physical examination showed no features of scleroderma or skin necrosis of her right hand. Both radial pulses were strong and symmetrical. Her nailfolds were visibly normal. The extractable nuclear antigen panel and other blood investigations were negative for scleroderma and other possible causes of secondary Raynaud’s phenomenon. Occupational or environmental factors were also excluded. Dermatoscope examination of the nailfolds revealed some areas of dilated capillary loops, areas of vascular sparing and proximal nail fold telangiectasia. The diagnosis of secondary Raynaud’s phenomenon was made, and an oral calcium channel blocker was started. The patient had significant improvement in symptoms shortly afterwards.

Background

Raynaud’s phenomenon is a well-known manifestation of excessive cutaneous vasoconstriction, most commonly secondary to cold exposure. It can be a primary disease or secondary to an existing connective tissue disease. The latter is commonly encountered in systemic sclerosis (SSc) and is associated with more severe presentation and complications such as ischaemia and gangrene. We report a case of Raynaud’s phenomenon in a patient with psoriatic arthritis (PsA).

Case presentation

A middle-aged right-handed housewife presented with complaints of painful hand discolouration for 1 week. The symptoms occurred sporadically but worsened when her hands were exposed to a cold environment, that is, when she reached for food inside the refrigerator. She described her hands changed colour when the symptom occurred. The pain was most severe when her hands became pale and subsided when the colour changed to blue and then red (figure 1).

Figure 1.

Comparison of both hands during the attack. The left hand (A and B) appears normal except for the ring and little fingers which appear pale. Note the deformity of the ring and little finger distal Interphalangeal (DIP) joints secondary to psoriatic arthritis (A). The right hand shows bluish-red discolouration of the fingers (C and D). Note the tip of the little finger is still pale (D).

She was diagnosed with plaque psoriasis with PsA 6 months earlier. She presented with severe pain over her left finger joints, early-morning stiffness and swelling for 3 months. She also had pruritic scaly erythematous plaques over her bilateral ankles and knees for 1 year. Her left-hand radiograph showed ring and little fingers’ sclerotic joint margins with narrowing of the joint spaces and marginal osteophytes. Her skin biopsy showed epidermal parakeratosis with elongation of the rete ridges, epidermal spongiosis and papillary dermis small capillary proliferation with lymphocytic infiltrate. She had fulfilled the Classification of Psoriatic Arthritis (CASPAR) diagnostic criteria that require at least 3 points: skin psoriasis, 2 points; dactylitis, 1 point and negative rheumatoid factor (RF), 1 point. She did not fulfil the following the CASPAR criteria: nail lesions (onycholysis, pitting or hyperkeratosis), 1 point and juxta-articular bone formation (distinct from osteophytes), 1 point.¹

Her joint pains and skin rash improved after taking oral methotrexate 15 mg weekly and topical clobetasone butyrate 0.05%. Her Disease Activity Index for Psoriatic Arthritis score was 5.²

Physical examination showed no features of scleroderma or skin necrosis of her right hand. Both radial pulses were strong and symmetrical. Her nailfolds were visibly normal.

Investigations

The extractable nuclear antigen panel, including Jo-1, Scl-70, PM/Scl, Ku, PCNA, Mi-2, nucleosome, histone, SmD1, P0/RPP, CENP-B, AMA M2, SS-A/Ro 60, SS-A/Ro 52, SS-B/La and U1-snRNP (enzyme immunoassay method), was negative for scleroderma, systemic lupus erythematosus (SLE) and other connective tissue diseases. The serum RF, antinuclear-antigen antibody and anti-double-stranded DNA antibody were negative as well. Her thyroid function test, complement C3 and C4 levels, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. There were no cervical ribs on her chest radiograph.

Nailfold dermoscopy using DermLite DL4 (3Gen, San Juan Capistrano, USA) revealed some areas of dilated capillary loops, areas of vascular sparing (figure 2A) and proximal nail fold telangiectasia (figure 2B).

Figure 2.

Nailfold dermatoscopy. Some areas of dilated capillary loops (white arrow), areas of vascular sparing (black arrow) (A) and proximal nail fold telangiectasia (arrowhead) (B).

Differential diagnosis

We consider our case to be secondary Raynaud’s phenomenon instead of primary due to painful, asymmetric attacks as symptoms, age onset of more than 40 years old as a risk factor and abnormal capillaroscopy as a sign.³

Secondary Raynaud’s phenomenon is more commonly seen in patients with SSc. Other less common causes of secondary Raynaud’s phenomenon include rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), inflammatory muscle diseases, SLE, Sjogren’s syndrome, vasculitis, cryoglobulinemia, Buerger’s disease and hypothyroidism.⁴

SSc is characterised by skin and internal organs fibrosis, vasculopathy and the presence of specific autoantibodies. It is divided into two subsets: limited and diffuse SSc. The former, which affects only acral parts of the body, has a relatively good prognosis with a 90% 10-year survival rate.⁵ The latter has a poorer prognosis due to progressive skin and various organ involvement. Five per cent of patients have typical symptoms of SSc without apparent skin fibrosis, that is, SSc since scleroderma. The earliest signs are Raynaud’s phenomenon and fatigue. The presence of Raynaud’s phenomenon, scleroderma pattern on capillaroscopy and SSc-specific antibodies predict a 65.9% chance of transition to definite SSc after 5 years.

Other systems involved in SSc are the gastrointestinal tract (eg, microstomia, xerostomia and dysphagia), nervous system (eg, headache, convulsions and ischaemic syndromes), musculoskeletal system (eg, tendinopathy, joint contractures and arthritis), cardiopulmonary system (eg, pulmonary arterial hypertension, myocardial fibrosis and coronary heart disease) and kidney (eg, scleroderma renal crisis and chronic kidney disease).⁵ The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2013 diagnostic criteria aid in the diagnosis. A minimum score of 9 is needed. Features assessed in the criteria include bilateral skin thickening proximal to metacarpophalangeal joints, finger skin thickening, fingertip lesions (pitting scars and tip ulcers), telangiectasis, abnormal nail fold capillaries, Raynaud’s phenomenon, lung disease (interstitial lung disease or pulmonary artery hypertension) and SSc-specific antibody status.⁶

RA is a systemic autoimmune disease with articular and extra-articular involvement. Typically, the patient presents with swollen and tender joints, usually affecting the small joints, morning joint stiffness and abnormal inflammatory markers such as increased ESR and CRP. MCP, proximal interphalangeal, second till fifth metatarsophalangeal, thumb interphalangeal and the wrists are the small joints affected in RA.⁷ The EULAR 2010 criteria aid in diagnosing RA. Patients fulfilling at least 6 out of 10 criteria from 4 domains are defined as having ‘definite RA’. The four domains are the number and site of involved joints, RF or anti-citrullinated protein antibodies status, ESR, CRP level and symptoms duration. Diagnosing RA in its early stage is challenging as patients may not fulfil the diagnostic criteria; hence, clinicians need to approach patients comprehensively. Early detection and treatment prevent irreversible joint damage and other complications such as vasculitis and interstitial lung disease.⁸

MCTD is a rare disease (1.9 per 100 000 population) characterised by the overlapping of at least two connective tissue diseases (CTD), which include SLE, SSc, polymyositis and dermatomyositis. It commonly affects women (84% of the population) with a mean age of 48 years at diagnosis.⁹ MCTD diagnosis should fulfil the Alarcon Segovia criteria which include positive anti-U1 RNP antibodies and at least three of the following symptoms: digital swelling, Raynaud’s phenomenon, synovitis, myositis or acrosclerosis.¹⁰ A newer revised Japanese diagnostic criteria include organ involvement such as pulmonary artery hypertension, aseptic meningitis and trigeminal neuropathy.¹¹

Apart from diseases, occupational and environmental factors should be considered as causes of Raynaud’s phenomenon. These include exposure to polyvinyl chloride, occupation or recreational cold exposure, exposure to vibration and repetitive hand trauma. History of carpal tunnel syndrome should be considered as well.¹²

Medications and toxins that may precipitate Raynaud’s phenomenon are chemotherapeutic drugs (cisplatin and bleomycin), interferon, oestrogen, sympathomimetic agents, ergotamines, clonidine, nicotine and narcotics.¹²

Patients with PsA present with arthritis, dactylitis, enthesitis and axial involvement, in addition to skin and nail diseases. Up to 15% of patients may not have psoriasis on presentation.¹³ PsA may mimic RA, crystal arthropathy and other inflammatory arthritides; hence, a prudent clinical review is necessary. The CASPAR criteria aid in the diagnosis. Features assessed in the criteria are evidence of psoriasis (current psoriasis, personal or family history of psoriasis), psoriatic nail dystrophy (onycholysis, pitting and hyperkeratosis), negative RF, dactylitis and juxta-articular new bone formation on radioimaging. The CASPAR criteria performed well in a retrospective study with a sensitivity of 99.7% and specificity of 99.1%.¹⁴

Our patient did not fulfil any of the aforementioned CTD diagnostic criteria except for the CASPAR criteria and had no drug, occupation and environmental factors that are linked to Raynaud’s phenomenon.

Treatment

Secondary Raynaud’s phenomenon was diagnosed and she was started on oral amlodipine 5 mg daily.

Outcome and follow-up

Raynaud’s phenomenon resolved shortly afterwards and never recurred during follow-up.

Discussion

Raynaud’s phenomenon involves exaggerated cutaneous microvascular response to cold and emotional stress, leading to vasoconstriction of the arteriovenous anastomoses and the adjoining nutritional capillary blood flow. The latter is normally protected from vasoconstriction during cold exposure. Vasoconstriction leads to the characteristic colour change of the hands and is more severe in secondary Raynaud’s phenomenon, especially if it is related to SSc. The SSc-related Raynaud’s phenomenon can frequently lead to ulceration, scarring or gangrene of the extremities.¹⁵

There are two proposed mechanisms of nailfold capillary changes in PsA. The first mechanism is the result of enthesitis (inflammation of the tendon and ligaments attached to the bone) causing local inflammation at the distal IP joints and the synovioenthesial complex (extensor and flexor tendon attachments and nail matrix). The second mechanism is elevated inflammatory cytokines levels (TNF, IL-17A and IL-23), which result in inflammation, dysfunction and apoptosis of vascular epithelial cells.¹⁶

Capillaroscopy is part of the diagnostic test for primary Raynaud’s phenomenon. Abnormalities of the nailfold capillary pattern (capillary dilatation and area of avascularity) and SSc-specific autoantibodies are independent risk factors for SSc.³ Nevertheless, nailfold capillary patterns associated with non-SSc-related secondary Raynaud’s phenomenon are unknown due to the rarity of the condition. Despite being the gold standard in capillaroscopy, high-magnification nailfold videocapillaroscopy (NVC) is costly and limited to specialist centres.¹⁷ Our hospital did not have the service. An alternative method is using dermatoscopes or ophthalmoscopes. Dermatoscopes’ performance in assessing nailfold capillary abnormalities is comparable to NVC, but less sensitive in terms of severity grading.¹⁸

Calcium channel blockers are well-established drugs for the treatment of patients with Raynaud’s phenomenon who do not respond to avoidance of triggers alone. Other suggested medical treatments include alpha-1-receptor antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, serotonin reuptake inhibitors, phosphodiesterase V inhibitors, nitrates, endothelin receptor antagonists and prostaglandins. The latter is the mainstay treatment for patients with digital ulceration and critical ischaemia. In patients who do not respond to medical therapy, digital (palmar) sympathectomy should be considered.¹⁵

To the best of our knowledge, this is the first documented case of PsA-associated Raynaud’s phenomenon. We have confidently excluded other secondary causes of Raynaud’s phenomenon based on the history, clinical features and laboratory investigation that we sent. This observation adds further to the body of knowledge of Raynaud’s phenomenon, a well-known but incompletely understood disease.

Learning points.

• Secondary Raynaud’s phenomenon is commonly associated with connective tissue diseases, most commonly SSc. Its association with psoriatic arthritis has never been documented before.

• Capillaroscopy serves as an important tool to differentiate primary and secondary Raynaud’s phenomenon.

• Further research is needed to explore the potential association between PsA and Raynaud’s phenomenon.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).