diagnostic strategy in rheumatology

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Eular On-line Course on Rheumatic Diseases module n1Jos A.P. da Silva, Karen Lisbeth Faarvang, Catia Duarte

DIAGNOSTIC STRATEGY IN RHEUMATOLOGY

Jos da Silva - Karen Lisbeth Faarvang - Catia Duarte

LEARNING OUTCOMES

Global objectives

At the end of this chapter the student will be able to differentiate the main rheumatological syndromes,

generate short representations of clinical cases and use them as guides for a structured approach to

questioning and physical examination of the patient and as a framework for final diagnosis.

Specific objectives

Recognize the importance of case representation, summaries and illness strings

Differentiate the main syndromes in rheumatology based on appropriate questioning and

physical examination

Generate short summary descriptions (representations) of clinical cases

Use the syndromes to guide questioning and clinical reasoning (Two-step diagnosis)

Differentiate inflammatory arthritis from osteoarthritis Recognize atypical osteoarthritis

Differentiate the different causes of regional syndrome

Characterize the most commons patterns of arthritis and their differential diagnosis

Recognize fibromyalgia

Differentiate the most common connective tissue diseases

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Index

THE BASES OF DIAGNOSTIC REASONING

The two-step approach to diagnosis

MAIN SYNDROMES

Regional syndrome Periarthcular Pain Joint Pain Neurogenic Pain Referred Pain

Generalized pain syndrome

Low back and neck pain

Articular syndrome

Osteoporosis syndrome

Bone syndrome

Muscle syndromeSystemic syndrome

Paediatric syndromes

FUTHER EXPLORATION OF ARTICULAR SYNDROMES

Patterns of degenerative joint disease

Patterns of inflammatory joint d isease Monoarthritis

Acute monoarthr it isChronic monoarthritis

Chronic symmetrical additive peripheral polyarthritis Chronic asymmetrical oligo/polyarthritis Ar thri tis of limb gird les Acute ol igo- or polyarthr it is/Febrile arthr it is / Arthri tis wi th manifestations

of the skin and mucous membranes Inflammatory low back pain Polyartritis with systemic manifestations

THE OPTIMAL ENQUIRY AND EXAMINATION IN RHEUMATOLOGY

Focus on relevant issues

Assess the validi ty of in formation

Listen to the patient

Examine properly

Weight your words. Summarize the data

THE ROLE OF LABORATORY TESTS IN RHEUMATOLOGY

KEY SUMMERY POINTS

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THE BASES OF DIAGNOSTIC REASONING

Educational research has shown that the main difference between a novice and an expert in clinical

diagnosis resides not on knowledge (the trainee may be at the highest level in this respect) but on

speed and agility during the diagnostic process. This is based on the ability of the expert to recognize

patterns and to identify clues and follow trains of thought. To abstract representations of diseases and

syndromes that shortcut precise pathways of reasoning, thus leading to a faster end result. The

expert follows a map, the novice is building one!

Research suggests that expert clinicians have their clinical knowledge organized around patterns or

illness scripts 1,2 strongly connected to summary problem representations. This non-analytic

reasoning, guided by scripts, concepts and representations, is an essential component of expertise in

diagnosis.

We can think of no better way to convey these concepts than by using Judith Bowens recent paper

on clinical reasoning published by the New England Journal of Medicine. 3

The author departs from a hypothetical clinical case and its description by a novice and anexperienced resident.

Patients history:My knee hurt me so much last night, I woke up from sleep. It was fine when I went

to bed. Now its swollen. Its the worst pain Ive ever had. Ive had problems like this before in the

same knee, once 9 months ago and once 2 years ago. It doesnt bother me between times.

Novice residents presentation:My next patient is a 54-year-old white man with knee pain. It started

last night. He does not report any trauma. On examination, his vital signs are normal. His knee is

swollen, red, and tender to touch. It hurts him a lot when I test his range of motion. Hes had this

problem twice before.

Expert residents presentation: My next patient is a 54-year-old white man with a sudden onset of

pain in his right knee that awakened him from sleep. He does not report any trauma and was

essentially asymptomatic when he went to bed. His history is remarkable for two episodes of similar,

severe pain 9 months and 2 years ago. He is pain-free between episodes. He is afebrile today. His

knee is swollen, tender to touch, and erythematous.

Consider the main differences between the two presentations.

As noted by Bowen, the novice resident transformed the patients story a little but without any

particular structure. Key elements of the Clinical Diagnostic Reasoning Process are not apparent orstructured.

The expert resident transformed the patients story into a meaningful clinical problem, an early

impression. This can be designated as the problem representation. It is an extremely important early

step of the diagnostic reasoning process.

1Eva KW. What every teacher needs to know about clinical reasoning. Med Educ 2005;39:98-1062

Elstein AS, Schwarz A. Clinical problem solving and diagnostic decision making: selective review of the cognitiveliterature. BMJ 2002;324:729-32.3Bowen, J L. Educational Strategies to promote clinical diagnostic reasoning. New Engl J Med 355;21:2217-25, 2006.

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This first representation guided his choice of additional questions and helped focus his clinical

examination. The patients words are translated into abstract , clinically relevant, terms. Last night

becomes acute onset, Ive had this problem before becomes recurrent, ...3 .

He presented a succinct summary of findings, which was dense in relevant information, highlighting

the defining features of the condition and the features that helped discrimination from alternative

diagnosis.His description, made into one sentence might have been this: Acute recurrent monoarthritis in an

otherwise healthy middle-age man. Of course adequacy and precision of language are absolutely

crucial for the efficacy of the process.

Although clinicians may not be aware of this process, the summary description, representation of the

problem helps to elicit the relevant information from memory and guides the subsequent diagnostic

workout. The inability to produce appropriate problem summaries and representations will result in the

exploration of multiples diagnostic hypotheses derived from isolated findings. A wrong summary will

lead to wrong diagnosis.

For this reason, the reader is strongly stimulated to exercise his/her ability to scrutinise andsummarize information, checking for its validity, as the clinical exploration evolves.

The two-step approach to diagnosis.

In the end we all follow a map, a route of non-analytic reasoning. Being aware of it will hopefully

guarantee that it is based on evidence and solid experience rather than misconceptions or

unquestioned common wisdom. Although experience is considered indispensable to design your own

map this chapter attempts to offer an example of one, in trying to call the readers attention to his/her

own map and the need to regularly check its accuracy.

Please be sure to be critical all the way, starting by the map we are offering you! We are sure you can

improve it!

We propose a two-step approach to diagnosis4. The first step aims to define the generic type of

pathology, that is, to set a main syndrome. Using the travel analogy we could say that these main

syndromes are neighbourhoods in rheumatology town. Step two involves a more detailed

investigation which is adapted to each syndrome and aims to differentiate between potential causes

of that syndrome, thus making a final differential diagnosis.

This approach allows us to identify precisely the main defining characteristics of each main syndrome

and the most important clues to differentiate between similar conditions and evaluate their severity.

This is what finally really matters for your clinical decisions. These should, obviously, be the guides

and focus of our strategic questioning and examination. The practicing clinician should be as precise

and detailed as possible on aspects that should matter to his reasoning and decision while trying to

be economic and fast on dismissing background noise.

Hopefully, this will help the reader to build and maintain a faster and reliable map for clinical expertise

in rheumatology.

4Reumatologia Prtica. JAP da Silva. Diagnosteo, Publishers. Coimbra. Portugal. 2004.

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MAIN SYNDROMES

The aim of our first step is to establish the main syndrome which is most representative of our

patients clinical picture (pattern recognition). The main syndromes proposed below represent our

diagnostic strategy, matured and revised over the years. Other experts may identify other operating

patterns deemed useful for their clinical practice.

Figure 1- Main rheumatological syndromes5

Figure 1 presents a short list of the nine main syndromes we propose as a way of organizing the first

step of diagnosis. In the following text we will explore the core characteristics of each syndrome and

its differentiation from others.

We will leave the final steps of the clinical diagnostic pathway to the individual chapters dealing with

specific conditions.

It is important to keep in mind that individual syndromes are not mutually exclusive. The presence of

one pattern does not exclude another. Rheumatic diseases are extremely variable in their

presentation: different syndromes may be suggested in consecutive patients with the same disease.

Seronegative spondyloarthropathies, for example, could present with oligoarthritis in one case and

with pure low back pain in the next. In some other cases periarticular involvement or polyarthritis will

dominate the picture requiring completely diverse differential diagnosis workouts. Our map must be

flexible enough to allow for this variability and we must make sure that neon signs suggest the

5Published under permission. Diagnsteo, Publishers. Coimbra, Portugal.

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Joint Pain

A lesion that affects a single joint will, obviously, result in a regional syndrome. The pain is related to

the use of the joint. Contrary to periarticular lesions, however, all movements tend to cause pain.

Physical examination will also show pain in all movements, with active and passive movements being

similarly painful. Passive joint motion is frequently limited due to swelling or structural damage.

Resisted movements do not cause exacerbated pain (as expected: the joint remains still during such

manoeuvres). Affected joints are frequently tender on palpation along the joint margins. Crepitus,

swelling, effusion and articular heat can, when present, make the involvement of the joint obvious.

Neurogenic Pain

Neurogenic pain is caused by the compression or irritation of nerve roots or peripheral nerves.

Sciatica, carpal tunnel syndrome and ulnar nerve syndrome are the most common examples in

practice.

Neurogenic pain is typically disaestesic (burning, tingling, numbness, electric shock), and affects the

sensitive area of a particular nerve or root. Pain derived from root lesions is exacerbated by

mobilization of the affected spine segment or, more rarely, by Valsalvas manoeuvre.

In the absence of associated pathology, regional musculoskeletal examination is normal. Guided

neurological examination is the key to the diagnosis (e.g.: sensibility, muscle strength, straight leg

rising, Tinnels test, tendon reflexes). Because detailed neurological examination is not routinely

performed by many physicians, the diagnosis can be easily missed if the enquiry fails to elicit the

clues. Keep in mind that muscle atrophy (as in carpal tunnel syndrome) and loss of pinprick sensation

are late features in root lesions and nerve compressions.

Referred Pain

Referred pain refers to symptoms felt at a distance from their anatomical origin. Localized

musculoskeletal pain can be referred from internal viscera or , more rarely, other joints.

The pain has uncharacteristic rhythm, more affected by the physiology of the viscera than by joint

movement and may be accompanied by suggestive symptoms. Local examination is normal.

Figure 2 shows the most common sites of musculoskeletal pain of visceral origin.

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Figure 2- Most common sites and origins of referred pain

Table n1- Distinctive features of regional syndromes

PeriarticularPain

Ar ticu lar pain Neurogenicpain

Referred Pain

Enquiry Selective painfulmovements

All jointmovements are

painful

Disaestesic.Aggravated by

compression ofnerve ormobilization ofthe spine

Unrelated tomovement.

Visceral timing

Pain onmotion

Active> passive.Selected motions

Active ~ passiveSeveraldirections

Normal. If rootpain: Pain onmotion of theaffected spinesegment

Normal

Range ofMotion

Active motion canbe limited bypain. Passive

motion: full

Can be limited inactive andpassive motion

Normal Normal

Resistedmobilization

Pain on specificmanoeuvres

No effect No effect No effect

LocalPalpation

Pain uponaffected structure

Possible:Crepitus,swelling, effusion,heat.Pain along jointmargin

Normal Normal

Neurologicalexamination

Normal Normal May beabnormal

Normal

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Generalized Pain Syndrome

In this syndrome, pain affects different parts of the body diffusely and imprecisely, with little or no

focus on joints.

Fibromyalgia accounts for the majority of the cases of generalized pain syndrome. Patients often use

or agree with the expression pain all over. Pain is often migratory and worse after, rather then

during, exercise. Exposure to cold and stress are frequently recognized as aggravating factors. It is

common that other symptoms are present like stress headaches, migraine, irritable bowel syndrome,

tight chest, depression, insomnia.

Fibromyalgia patients may present with different patterns of dominant symptoms, which can be

misleading. Not rarely, these patients are misdiagnosed and treated for a variety of conditions,

including rheumatoid arthritis, ankylosing spondylitis, disc herniation, etc. These patients must be

carefully examined to discard joint inflammation, neurological abnormities and any other possible

explanation for their complaints. Laboratory tests and imaging should be normal or at least

inadequate to explain the symptoms.

The wise clinician will keep in mind the limitations of the existing criteria for fibromyalgia, especiallywith respect to the tender point count. Other rheumatic and metabolic conditions may involve

widespread pain above and below the waist bilaterally: rheumatoid arthritis, systemic lupus

erythematosus, Sjgrens syndrome, polymyalgia rheumatica, ankylosing spondylitis, polymyositis,

hypothyroidism, hypoparathyroidism, polyneuropathy, debilitating systemic diseases. Careful

questioning and examination together with minimal investigation is usually sufficient to clarify the

diagnosis.

The association of fibromyalgia with any other rheumatic condition is common and represents some

of the most difficult clinical situations in rheumatology.

Low Back And Neck Pain

Back and neck pain is extremely frequent in medical practice. However, the vast majority of cases will

escape precise aetiological diagnosis even after meticulous investigation. This is due to the

complexity of the spine, muscles, ligaments, nerves and supporting soft tissues in the area leading to

a multiplicity of potential causes. The contribution of current diagnostic methods to clinical diagnosis is

very limited. The correlation between even sophisticated imaging and clinical manifestations is poor.

Used inappropriately, imaging can, actually, lead to more problems than solutions in this area.

We know that in the vast majority of cases it will be impossible to make a precise diagnosis and

therapy will be guided by general rules of pain management, exercise and risk factor control. Only a

small percentage of cases involve a specific aetiology requiring special diagnostic and therapeuticaction. However, the underlying causes are potentially treatable and can be life-threatening, such as

metastases and infection. They cannot be missed!

The first group can be designated as non-specific low back pain or non-specific neck pain.

Faced with subjective information and unreliable investigations, the wise clinician will focus on clinical

manifestations, pain intensity and disability, more than aetiology, while keeping a careful vigilance for

any clues that may suggest a potentially serious and/or treatable cause for each individual case.

The most recommended strategy for back and cervical pain is based on the search and recognition of

alarm symptoms and signs, red flags that indicate a higher probability for an underlying specific

cause. Table 2 summarizes the most common causes of low back pain, according to the presence or

absence of red flags.

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Table n2 - Common causes of low back pain, suggestive manifestations and red flags.

Red Flags

Back pain with inflammatory rhythm

Localized pain

Nocturnal painVisceral or constitutional symptoms

Onset before age 30 or after 50

Pain at movement in all directions

History of neoplasm

Risk or evidence of osteoporosis

Neurological manifestations

Sacroiliitis

Spondylodiscitis

Metastases

Osteoporotic fracture

Neurogenic pain

Referred pain

Interspinous ligamentitis

No Red flags Acute mechanical low back pain

Chronic mechanical low back pain

Fibromyalgia

In most cases the pain has a mechanical rhythm. It is triggered by movement and relieved by rest. In

adults, most of these conditions are caused by spondyloarthrosis. In many other cases, particularly in

young people, there is no apparent cause for the pain, and it is thought to be the result of mild

articular instability and irritation of the nerves and muscle bundles leading to painful reflex muscle

contractions. Both situations should be treated conservatively, aiming to relieve the pain and restore

function, without any specific aetiological intervention. In a few cases, the pain may be neurogenic,

inflammatory, infectious, neoplastic or psychogenic in origin. The clues for such special conditions are

similar to those described above. The possibility of referred pain, from the heart, lung apex andshoulder must be kept in mind. Acute lymphadenopathy, thyroiditis and meningitis represent important

non-rheumatic causes of neck pain.

Ar ticu lar Syndrome

Arthropathies, i.e., diseases affecting the joints, are at the heart of rheumatology. Final diagnosis will

involve the identification of a specific disease, the evaluation of its activity, accumulated damage,

functional impact and prognosis.

On the first stepwe have to recognize that this is an articular syndrome. As described above, this is

suggested by pain that emerges with virtually all movements of the joint (as opposed to selective pain

found in periarticular lesions). Patients can usually locate the pain precisely over the joint(s) involved

(as opposed to muscle or diffuse pain, as in muscle disease or fibromyalgia). On examination, pain

has similar intensity with active and passive mobilization and both can be limited in range (passive

motion should not be limited in purely extra-articular lesions). Resisted movement will not affect the

pain. Palpation will typically cause pain along margins of the joint. The presence of crepitus, heat,

swelling or effusion of the joint will confirm the articular origin of the problem.

On the second step, the most important goal is to evaluate the clues of degenerative versus

inflammatory joint disease. Enquiry and physical examination are critical in this respect.

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Degenerative joint disease (osteoarthritis) is typically associated with mechanical pain: pain that

increases with repeated use of the joint and is worst at the end of day. Pain intensity decreases

during rest, is rarely present at night and the patient can usually find a pain-free position. Patients can

describe that pain increases again after resting and this may be accompanied by gelling, stiffness

that subsides in 2-3 minutes. Early morning stiffness associated with degenerative arthritis ceases in

a few minutes (


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Osteoporosis Syndrome

This is characterized by the presence of risk factors for osteoporosis. Although not a real syndrome

we believe this is a useful construct as osteoporosis is a common disease and the ideal time for

intervention is before any symptoms occur. It is, therefore, important to search for risk factors and

take proactive action including preventive measures, bone densitometry or other investigations, as

appropriate.

Risk factors for osteoporosis and fractures include post-menopausal status, early menopause, late

menarche, low weight and height, prolonged gluococorticoid therapy, sedentary lifestyle, insufficient

intake of dairy products, family history of osteoporosis or fracture. Treatment with glucocorticoids

deserves special attention by rheumatologists. Some diseases can lead to secondary osteoporosis,

including hyperthyroidism, hyperparathyroidism, malabsorption, chronic alcoholism and liver disease.

In almost all cases osteoporosis should be identified as a side issue, thanks to the physicians

consideration of relevant factors in a patient that consults for a totally different reason.

Bone Syndrome

It is characterized by deep, diffuse, continuous pain, unrelated to movement. Frequently pain will be

worse at night and disturb the patients sleep. More commonly it will affect the spine, pelvis, and the

proximal segments of the limbs. The local examination is usually normal.

These features should raise the hypotheses of bone tumours, metabolic bone diseases or

inflammation of the periosteum. Metastatic tumours are the most common neoplasms of bone and

bone is the third most common site of metastasis after lung and liver. Pain due to a metastatic lesion

may be the first symptom of the underlying malignancy.

Muscle Syndrome

The pathological involvement of muscles is most commonly reflected by predominantly proximal

weakness and muscular atrophy. Myopathic patients may have difficulty going up and down stairs,

getting up from a low chair or combing their hair but their handshake is firm and they can walk on

tiptoe. Neurological examination may show decreased proximal muscular power, and muscle

tenderness. Muscle atrophy is a later and inconstant finding.

Polymyositis, dermatomyositis and inclusion-body myositis are the most typical causes of this pattern.

Arthralgia and low-grade arthritis may also occur, especially when inflammation of muscle occurs as

part of a connective tissue disease, such as systemic sclerosis or mixed connective tissue disease.

Differential diagnosis of adult polymyositis must include a broad array a conditions capable of

affecting skeletal muscle.

Hypothyroidism, sarcoidosis and especially osteomalacia must be considered in this clinical context,

as the myopathy associated with these conditions may dominate the clinical presentation.

Muscle pain and stiffness of the proximal limb girdles, characteristic of polymyalgia rheumatica may

be interpreted as myopathy. The confusion may be increased in the case of giant cell arteritis,

because of constitutional fatigue and weakness.

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Rheumatologists should also give special attention to commonly used medications which can cause

neuromuscular complications, including glucocorticoids, hydroxychloroquine, colchicine, cyclosporine,

statins and fibrates among many others.

Non-inflammatory myopathies must also be considered and they include an enormous variety of

neurological conditions such as spinal muscle atrophies, myasthenia gravis, myotonic diseases,

congenital myopathies and storage diseases.

Systemic Syndrome

All inflammatory joint diseases may be accompanied by extra-articular manifestations, involving other

organs and systems. Looking for these extra-articular clinical manifestations is therefore a critical part

of the investigation of rheumatic conditions. In many cases, these manifestations occur together with

polyarthritis, which may constitute the basis for our subsequent differential diagnosis. In some

patients these manifestations clearly dominate the clinical picture thus establishing a systemic

syndrome as the best basis to further explore the diagnosis.

The most common and relevant manifestations are presented in Table 3.

Connective tissue diseases are the most common causes of systemic syndrome. Their distinction is

based on the predominant clinical manifestations of each disease (Table 4). The clinician must,

however, exercise flexibility here as overlap between different diseases is extremely common.

Vasculitis includes a large number of different conditions with proteomic manifestations. This is further

explored in a dedicated discussion in this module.

Stills disease typically presents, in both children and adults, with a systemic syndrome dominated byfever, rash, weight loss and lymphadenopathy and leukocytosis in addition to arthritis. Serositis,

pneumonitis, hepatomegaly, myalgia may also be present in a complex multisystemic clinical scenario

demanding differential diagnosis with connective tissues diseases, vasculitis, malignancy and

infection, among others.

Occasionally, reactive arthritis may be dominated by extra-articular features, such as uveitis,

nephritis, carditis, gut and eye inflammation. Sarcoidosis should be especially considered in the

presence of lymphadenopathy, erythema nodosum, lung, eye or liver involvement.

Relapsing polychondritis, Familial Mediterranean fever may also deserve consideration in the context

of a systemic syndrome, but they are relatively rare and associated with suggestive features.

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Table n3- Main systemic manifestations associated with rheumatic diseases

Associated diseases(in descending order of frequency)

Constitutional manifestations

Fever

Weight loss

Severe fatigue

Systemic lupus erythematosus

Systemic sclerosis

Rheumatoid arthritis

Mixed connective tissue disease

Vasculitis

Skin manifestations

Photosensitivity

Skin rash

Scleroderma

Purpura

Livedo reticularis

Ulcers

AlopeciaTelangiectasia

Heliotrope

Gottrons papules


Systemic sclerosis

Dermatomyositis

Mixed connective tissue disease

Overlap syndromes

Vasculitis

Mucosal manifestations

Oral and genital aphthae

Dry eyes and mouth

Red eye

Balanitis

Sjgrens syndrome



Reactive arthritis

Ankylosing spondylitis

Behets disease and other vasculitis

Serositis Connective tissue diseases (SLE)


Raynauds phenomenon Idiopathic Raynauds phenomenon

Systemic sclerosis


MCTD

Arterial or venous thrombosis Vasculitis

Antiphospholipid syndrome

Recurrent abortion Antiphospholipid syndrome

Dysphagia Systemic sclerosis

Dyspnoea Connective tissue diseases

Lower limb oedema

hypertension

Connective tissue diseases

Lymphadenopathy Connective tissue diseases

Muscular weakness Myositis

Overlap syndromes

Convulsions

Psychosis

Peripheral neuropathy


Vasculitis

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Table n4 -Manifestations associated with the different connective tissue diseases. The number of

+ reflects the weight of the manifestation as an argument in favour of a diagnosis.In secondary anti-

phospholipid antibody syndrome Hypertensive crisis, drop in creatinine clearance.

Systemic

lupus

erythematosu

s

Systemic

sclerosis

Polymyositis

Dermatomyositis

Mixed

connective

tissue

disease

Vasculitis

Constitutional

symptoms

++ - + + +++

Ar thri tis +++ + + +++ +

Diffuse swelling

of the hands

Rare ++ Rare ++ -

Photosensitivity +++ + +++ + -

Cutaneous

sclerosis

- +++ - + -

Erythema ++ - ++ + -

Vasculitic

lesions

+ + Rare Rare +++

Raynauds + +++ + ++ +

Hair loss ++ ++ Rare Rare Rare

Sicca syndrome ++ ++ + ++ -

Uveitis

Serositis ++ - - ++ -

Ar ter ial and

venous

thrombosis*

+ Rare Rare Rare +++

Miscarriages* + Rare Rare Rare Rare

CNS + Rare Rare Rare +Muscular - + +++ ++ +

Digestive - ++ + ++ -

Haematological +++ - - ++ -

Renal +++ ++ Rare + ++

Pulmonary + ++ + ++ ++

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Paediatric Syndromes

Many of the rheumatic conditions that affect children are similar to adult diseases. However, some are

specific to children. All of them have special features that deserve consideration and must be seen in

a specific context of differential diagnosis. The enquiry and examination require an adapted strategy

and dedicated skills. For these reasons, the clinical approach to paediatric rheumatic syndromes is

addressed in an in-depth discussion in this module.

FUTHER EXPLORATION OF THE ARTICULAR SYNDROME

Once we establish that the patient has an arthropathy, it is useful and usually simple to separate

degenerative from inflammatory arthritis. The second step of diagnosis is helped by the consideration

of different patterns of presentation.

Patterns of degenerative joint disease

Typical osteoarthritis develops in middle age or elderly people and gets slowly worse over time.

Weight bearing joints like the hip, the knee and the spine are the most common sites of osteoarthritis.

Note, however, that the first carpo-metacarpal and the interphalangeal joints are commonly involved

whereas the ankles, are usually spared.

Nodal osteoarthritis is considered as a typical osteoarthritis. In this case, proximal and distal

interphalangeal joints of the hands are involved. It is often hereditable and is more common in middle

age and elderly women. Pain frequently presents a mixed rhythm and inflammatory flares are

common.

Typical osteoarthritis is common, strongly related with ageing, workload and genetic predisposition.

No specific cause can be identified (primary osteoarthritis).

Atypical osteoarthritisis suggested by odd characteristics, such as affection of younger patients

or uncommon locations such as the shoulders, elbows, or metacarpophalangeal joints. It tends to

develop faster than typical osteoarthritis.

Such features should alert the clinician to a suggestion of a secondary osteoarthritis e.g.

degenerative disease due to a specific cause, which should be identified and treated if possible (table

5).

Table n5- Most common causes of secondary osteoarthritis.

Fracture involving the articular surface Preexisting

arthritis

Meniscectomy Axial deviations

Articular instability Aseptic necrosis

Intra-articular loose bodies Chondrocalcinosis

Osteochondritis dissecans

Particularly demanding occupations

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Patterns of inflammatory jo int disease

The Inflammatory articular syndrome is suggested by pain with inflammatory rhythm and confirmed

by the demonstration of joint inflammation (diffuse elastic swelling around the joint with or without

redness and heat).

When evaluating a patient with arthritis, it is important to determine:

1) which joints are affected and their pattern of distribution,

2) how the condition began and how it developed over time

3) the presence or absence of inflammatory low back pain

4) accompanying extra-articular manifestations

Once you have this information, you may classify the arthritis according to a number of parameters,

which will help you find and support a final diagnosis:

Number of joints affected

Monoarthritis: one single joint involved

Oligoarthritis: 2 to 4 joints involvedPolyarthritis: 5 or more joints involved

Acute versus Chronic

Acute: onset in hours or days

Chronic: onset over weeks or months

Addi tive versus Migratory

Additive: the affected joints are added progressively

Migratory. The inflammatory process flits from one joint to another

Persistent versus Recurrent

Persistent: once it has set, the arthritis persists over the time

Recurrent: episodes or crisis of arthritis separated by symptom-free intervals

predominantly Proximal versuspredominantly Distal

Proximal: arthritis mainly involves large joints, i.e., proximal to the wrist or ankle, and the spine

Distal: the arthritis mainly involves the small joints of the hands and feet, with or without the wrist

and ankle

Symmetrical versus AsymmetricalSymmetrical: affects approximately the same joint groups of each side of the body

Asymmetrical: there is no relationship between the joints involved on either side of the body

With or without inflammatory low back pain

With or without systemic manifestations

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The appropriate use of this classification represents the most important step in the differential

diagnosis of arthritis. We suggest that you always try to represent your patients condition with as few

words as possible, making a problem representation in one sentence: e.g. asymmetrical

oligoarthritis, with inflammatory back pain or acute arthritis with fever and rash. This will make the

final diagnosis a lot easier and reliable. Below, we describe the most common patterns we use in

practice. Be critical of them: you may find that other patterns work best for you.

Monoarthritis

It is useful to separate acute (onset over hours or days) from chronic monoarthritis.

Acute monoarthr it is . The most common cause of acute monoarthritis is goutand trauma, but this

condition should be considered infectious until proven otherwise, because septic arthritisis rapidly

destructive and can be life-threatening if not properly treated.

The classical presentation of septic arthritis involves the rapid onset of intense pain, redness and

swelling in a single joint. Systemic symptoms like fever, malaise could be present. Note, however, that

onset may be prolonged over days and inflammatory signs may be relatively mild. When in doubt it is

wise to ask for bacterial cultures of synovial fluid.

Gout is the most common cause of acute monoarthritis. First episodes involve one of the first

metatarsophalangeal joints in 50% of cases. This is a remarkable feature that demands equal

consideration of the obvious alternative: another joint is affected in every second case! Pain has a

sudden onset, frequently at night, and reaches its maximum in a matter of hours. The affected joint is

typically swollen, bright red, hot and extremely tender. Systemic symptoms such fever and malaise

could be present.

Initial episodes of gout almost always follow a monoarticular recurrent pattern with symptom-freeintervals, predominantly in the lower limbs. With time, intervals become shorter, the upper limbs also

become involved and more than one joint can be affected in each episode, occasionally leading to a

polyarticular pattern.

Definite diagnosis of gout demands the demonstration of monosodium urate crystals in the synovial

fluid.

Other causes of acute monoarthritis include pseudo-gout(calcium pyrophosphate dihydrate disease)

and post-traumatic synovitis. Palindromic rheumatism, reactive arthritis, psoriatic arthritis and

bacterial endocarditismust also be considered. Reflex sympathetic dystrophycan pose difficult

differential diagnosis with acute and chronic monoarthritis

Chronic monoarthritis. Monoarthritis can have an indolent course, lasting from weeks to months.

The main possible causes include infection(brucella, mycobacterium, Lyme disease, others), crystal

induced arthritisand monoarticular presentation of oligo- or polyarthritis (juvenile idiopathic arthritis,

reactive arthritis, sarcoidosis, seronegative spondyloarhropathy).

Differential diagnosis must incorporate causes of non-inflammatory arthropathy, such as

osteoarthritis, recurrent hidrarthrosis, osteonecrosis, reflex sympathetic dystrophy, neuropathic

(Carchots) joints and tumours, including villonodular synovitis.

The aetiological diagnosis of chronic monoarthritis usually requires synovial biopsy with pathological

and bacteriological examination. Some reports suggest that PCR techniques should be employed to

identify latent infections. In a large number of cases, no specific cause can be identified.

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Chronic symmetrical additive peripheral polyarthritis

This pattern describes joint inflammation involving, simultaneously, five or more joints (polyarthritis),

for more than six weeks (chronic). Small joints of the hands and feet are predominantly affected, with

or without the wrist and ankle (peripheral), and approximately the same joints are involved on each

side of the body (symmetrical). The affected joints have been added progressively (additive). There

should be no inflammatory low back pain (see below).

The most common cause for this pattern is rheumatoid arthritis, and this is the most common

pattern of presentation for this disease. Onset of especially aggressive disease may be accompanied

by constitutional manifestations such as fever and lymphadenopathy. This could suggest a systemic

syndrome but articular manifestations dominate the clinical picture in the vast majority of patients.

Other systemic manifestations may occur but they are usually milder than arthritis, tend to occur later

in the course of disease and are becoming less frequent with timely and effective treatment of

rheumatoid arthritis.

This pattern of arthritis is common to other rheumatic conditions, especially other connective

tissue diseases, such as systemic lupus, primary Sjgrens syndrome, polymyositis and mixed

connective tissue disease. Psoriatic arthritiscan also present with this pattern (pseudo-rheumatoid

form) although it tends to be more asymmetric, and involve either the distal interphalangeal or the

sacroiliac joints. Differential diagnosis can be difficult but some would say that the presence of

rheumatoid factor excludes psoriatic arthritis. Chondrocalcinosisdeserves consideration especially

in older patients. A pre-existing pattern of degenerative disease with recurrent inflammatory episodes

may suggest this condition, but it is not always present. Polyarticular gout may have a similar

pattern of distribution. However the onset tends to be abrupt and it is almost invariably preceded by a

period of recurrent monoarthritisin the past. Viral arthritis, such as those associated with parvovirus

B19, HIV and hepatitis, may follow a similar pattern but tend to have a more acute onset than

rheumatoid arthritis or the connective tissue diseases.The clinical contribution to differential diagnosis relies on careful evaluation of extra-articular

manifestations. Several investigations may be useful for this purpose, depending on the clinical

scenario.

Chronic, asymmetrical oligo/polyarthritis

This describes an asymmetrical arthritis for more than 6 weeks (chronic), affecting 2 or more proximal

or distal joints (oligo/polyarthritis). Dactilitis or involvement of distal interphalangeal joints is a common

but not mandatory feature.Psoriatic arthritisis the most common cause of this pattern. Personal or family history of psoriasis

will provide support for this diagnosis. When the arthritis is limited to proximal and distal

interphalangeal joints, hand osteoarthritis needs to be considered as an alternative diagnosis.

Although this has usually a slow development, it may evolve with acute inflammatory flares of these

joints and cause erosions. Chronic sarcoid arthropathy may evolve with a similar pattern the

inflamed joint tends to show a nodular asymmetric aspect as opposed to the spindle shape of

psoriatic synovitis.

Other seronegative spondylarthropathies, such as ankylosing spondylitis, may also cause this

pattern of arthritis. Inflammatory back pain is expected in this condition but may not be obvious.

Reactive arthrit isor arthritis associated with inflammatory bowel diseasemay show this patternbut when distal joints are affected they usually adopt a symmetrical distribution.

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Other causes include incipient rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular gout,

pseudo-gout and Behets disease. Again, careful enquiry of axial and extra-articular manifestations

may provide critical clues to the diagnosis.

Proximal oligoarthritis

Patients may present with arthritis involving predominantly proximal joints. The most common causes

are the seronegative spondylarthropathies. A complete questioning and physical examination is

important to differential diagnosis. The presence of inflammatory low back pain, personal or family

history of psoriasis, inflammatory bowel disease, the occurrence of any infectious disease (infectious

diarrhoea, urinary tract infection) on the weeks preceding arthritis must be explored in the enquiry.

Other causes of proximal oligoarthritis include Behcets disease, juvenile idiopathic arthritis and

incipient rheumatoid arthritis. Not rarely, arthritis with this pattern defies formal classification and is

better described as unclassified oligoarthritis.

Ar thri ti s o f l imb g irdles

This is characterized by inflammatory pain with marked stiffness, affecting the hip and shoulder

girdles. Physical examination finds features of arthritis of the shoulder and/or hips, occasionally with

milder involvement of peripheral joints.

Polymyalgia rheumaticais the paradigm of this pattern of arthritis. The patient is typically an elderly

person, presenting with pain and stiffness in the neck, shoulders and hip area. Peripheral joints can

be involved. Some extra-articular manifestations must be explored in questioning. Malaise, fever,

fatigue, anorexia and weight loss are common features. Jaw claudication, temporal headaches and

loss of vision, suggest associated temporal arteritis.

Seronegative spondylarthropathies,incipient rheumatoid arthritisare alternative causes for this

pattern of arthritis.

Acute oligo-or polyarthr it is - Febri le arthr it is - Arthr it is wi th manifestations of the skin and mucousmembranes

This is characterized by arapid onset of oligo- or polyarthritis, often associated with a recent infection,

fever or changes in skin and mucous membranes.

This pattern suggests the possibility of reactive arthritis. In these cases, the patient is most often a

young adult male. The enquiry should explore the occurrence of a significant infection within the twoto three weeks prior to the arthritis. There is a wide variety of potential causal agents, but most

frequently this will be gastrointestinal, genitourinary or upper respiratory infection. Reactive arthritis is

frequently associated with manifestations in the skin (rash, erythema, pyoderma, plantar

keratoderma...) and mucosae (conjunctivitis, urethritis, oral or genital ulceration, circinate balanitis).

The pattern of articular involvement varies. Proximal oligoarthritis is the most common, but, for

example, post-viral arthritis is often polyarticular, symmetrical and distal.

Stills disease (in adults or children) is characterized by an acute or sub acute onset of arthritis,

associated with fever, evanescent skin rash, weight loss, lymphadenopathy and/or splenomegaly.

Systemic lupus erythematosus, dermatomyositis, Behcets disease and, occasionally,

rheumatoid arthritis, may present with similar features and should be considered in the differential

diagnosis.

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Inflammatory low back pain

This refers to low back pain that persists or predominates at night, does not relieve with rest but rather

with movement and is associated with prolonged morning stiffness. This is always a significant clue

that deserves clarification.

Inflammatory low back pain is a typical manifestation of seronegative spondylarthropathies:

ankylosing spondylitis, psoriatic arthritis, Reiters syndrome, spondylitis of inflammatory bowel

disease. It is also a feature of Behets diseaseand infectious or aseptic discitis.

In seronegative spondyloarthropathy the involvement of the spine is very common and could be

accompanied with peripheral joints involvement or not. When the condition is strictly limited to the

spine, ankylosing spondylitis becomes the most probable diagnosis. If peripheral joints are also

involved, the pattern of distribution and the associated manifestations are the key to the final

diagnosis. Psoriasis, inflammatory bowel disease, urethritis, conjunctivitis, uveitis, venous and arterial

thrombosis, and mucosal ulcerations must be explored in questioning and examination.

Polyarthritis with systemic manifestations

This is characterized by polyarthritis with clear manifestations or strong suggestion of compatible

systemic involvement.

Systemic lupus erythematosusis the most common cause but other connective tissue diseases

must be considered in face of this pattern of involvement.

Reactive arthrit isand viral arthritiscould present with polyarticular involvement and are associated

with systemic manifestations, although these are usually of a different nature. Stills diseasemay

deserve consideration under this pattern.

THE OPTIMAL ENQUIRY AND EXAMINATION IN RHEUMATOLOGY

Whether we are aware of it or not, we begin our differential diagnosis with our first question and then

test out, reinforce or eliminate hypotheses as the enquiry goes on. The ideal enquiry should be

economical and critical.

Focus on relevant issues

By economical we mean, short, limited to relevant issues while comprehensive: no relevant issues

should be left unexplored but irrelevant information should be discarded, and as soon as possible.

This is important not only because the typical physician is always short of time but most of all because

irrelevant information works as a distractor, as background noise, keeping your mind off what really

matters. Mastery of this crucial ability requires that the clinician has a very clear view of what

information makes a difference, what needs to be taken into account during the diagnostic process or

treatment selection. Let us use an example. The sequence of involvement of joints in a polyarthritis

makes no differences to the diagnosis: the interpretation of a chronic symmetric peripheral

polyarthritis is the same irrespective of the first affected joints being the feet or the hands, the wrists

or the MCP joints. This detail is therefore, irrelevant and should not be explored. We do not need toask for the rhythm of pain in individual joints involved in polyarthritis.

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However, we must do that regarding an associated back pain. In most cases this will be nonspecific

mechanical back pain with no added significance. On the contrary, low back pain with an

inflammatory pattern is a crucial clue to the interpretation of peripheral polyarthritis.

There is no absolute measure of the value of any piece of information that can be applied to every

clinical setting. Be critical about the importance we give to any features, explore your own thoughts on

this, be aware of your map and the signs that count within it. Focus on the issues that really matterfor your reasoning, and make your own problem representation in one sentence.

Assess the val id ity of information

To make the enquiry work in an optimal way it is also crucial that you critically appraise the validity

and the degree of certainty of each piece of information, question each partial conclusion and be

aware of its impact on your reasoning.

Your map is made of crossroads where you choice are guide by a signal or symptom. If you misread

a signal youre bound to take the wrong road to the diagnosis. Pay good attention, especially to signsthat drive you to a very different direction. Never forget to make an appropriate systems enquiry in

patients with inflammatory arthritis.

Symptoms and even signs are frequently poorly defined and subjective in Rheumatology. You cant

always be sure to have read signs precisely. This is inherent to this field but we would suggest two

ways to try and diminish the risks involved. One suggestion is that you discuss crucial symptoms with

the patient in different ways, using variable expressions until you are certain to have understood

exactly what the patient felt. It is very useful, for this purpose, to summarize your interpretation and

negotiate it with the patient.

This suggestion should stimulate you to keep an open critical mind on signals and symptoms that are

influential but not very precise. When facing one, do what you would do while traveling: explore one

direction, assuming the sign is real and reliable. Explore the alternative directions, i.e. different

interpretations of that sign.

Listen to the patient

The recommendations above, if taken too strictly, can make you run the risk of directing the

questioning so much, that your patients may not have an opportunity to express their main concerns.

This must be absolutely avoided. Addressing the patients concerns is obviously core to the objectives

of the clinical encounter. On top of that, patient clues will feed your lateral thinking, open your eyes

around predetermined scripts, and keep you from disregarding relevant issues that were not brought

up by your line of thought.

Examples are numerous and common: a patient describing pain and stiffness around the shoulders is

finally given an opportunity to refer his weight loss; back pain is finally related to a perforated ulcer

when we listen to the patients digestive complaints; unexplained pain is clarified when we allow

ourselves to listen to hints of anxiety and distress, etc. Give the patient a couple of minutes at the

beginning of the enquiry. This will give you an idea of the capacity of the patient and focus the

problem. Make sure that you hear the patients own story and not what other doctors have said.

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Literature has shown that specialists in ears, nose and throat interrupt their patients within 2 seconds

from the start of an enquiry; there is no reason to believe that rheumatologists do this differently.

Crucial information may, thus, be lost.

Keep vigilance over whether your strategy allows enough room for the expression of all relevant

information the patient may have for you. Be sure to always end your questioning by asking the

patient: is there anything else troubl ing you that I havent asked about?

Examine properly.

Physical examination will play a major role in clarifying the diagnosis. Examination is extremely

important to clarify the anatomical origin of the pain (articular, periarticular, muscle, neurogenic, etc),

and the nature of the disease (degenerative, inflammatory, entrapment, ). Once you have finished

enquiry, your mind will have a natural tendency to approach physical examination with a biased

tendency to confirm expectations. It happens with everyone but this is a common cause of error and

the wise clinician will keep it under scrutiny. If, before examination you are convinced that yourpatient has fibromyalgia, you may put slightly more pressure on the tender points, ignore doubtful

signs of joint swelling or forget to explore the sacroiliac joints.

Careful musculoskeletal examination can be performed in a short time and can be easily combined

with an adequate general examination. Although this examination is not technically demanding it must

be done with appropriate care and detail, or the diagnosis may be completely missed. Pain on

movement of the ankles can be arthritis or Achilles tendonitis, for example, tenderness due to

anserine bursitis may be wrongly taken as indicating arthritis, pronator syndrome will never be

diagnosed without the proper examination techniques, trochanteric bursitis can closely mimic

sciatica, etc. Counting joints and filling in protocols can actually drive you away from the actual

patient.

This is obvious, of course! However, we have been frequently surprised with the lack of examination

skills presented by advanced trainees and even experienced rheumatologists. The methods used to

examine the same joint or muscle vary enormously among physicians. Some are better than others. It

seems that many of us believe that clinical examination skills come naturally and few centers devote

any specific efforts to the teaching and assessment of examination skills. Well, be sure you are doing

it properly these are the very foundations of clinical excellence.

Weigh your words. Summarize the data.

We also suggest that you try to define each symptom or syndrome with as few words as possible. Be

aware of the exact meaning and implication of each word, on others and on yourself. Once you

decide or say that a patient has arthritis you allow yourself and others to exclude muscle pain or

periarticular lesions from consideration. Being aware of what it takes to say that a patient has arthritis,

you may consider using the word arthralgia, or inflammatory arthralgia, or arthropathy to refer to less

defined conditions. This exercise will help you to scrutinize the validity for each piece of data you use.

Using words that are as specific as possible, but only as possible, will enhance the precision of your

communication with others and of your own reasoning process.

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By summarizing the data you focus on what is relevant, diminish the impact of background noise

and enhance the clarity and efficiency of your reasoning. Of course, the background information will

still be there! You will still be able to recall the nuances of the symptoms or signs of the patient and

value these when needed in the diagnostic process. Most nuances are not crucial for diagnosis: there

is, for example, a certain temperature profile which is more typical of Stills disease but you should

think of this hypothesis in any patient with fever, arthritis and lymphadenopathy. Nuances that arereally important should be part of your summarized description, anyway.

While traveling through clinical exploration the physician must have split mind: one part is interacting

and keeping the empathy with the patient, the other is checking the map, the quality and relevance of

signs and what direction the journey is taking.

THE ROLE OF LABORATORY TESTS IN RHEUMATOLOGY

Laboratory tests have limited utility in the diagnosis of most rheumatic conditions. Their influence

varies according to the clinical scenario and they should, obviously, be chosen to clarify clinically

supported hypothesis. Ordering a battery of laboratory tests will more frequently introduce false-

positive information, noise and cost than clarify the diagnosis.

The ability of a test to classify individuals correctly as having or not having a given disease depends

on sensitivity and specificity.

Sensitivityis the proportion of true positives (i.e., true patients)that are correctly identified as such

and is, therefore, equal to 1 minus the false negative rate. Specificity is the proportion of true

negatives (i.e. no-patients)that are correctly identified as such and is, therefore, equal to 1 minus the

false positive rate.

Specificity is profoundly affected by the population used to establish it, i.e., the number and medical

conditions of the control population. For example, rheumatoid factor prevalence in the general healthypopulation increases with age and is associated with a variety of non-rheumatic conditions (such as

endocarditis and tuberculosis) and rheumatic diseases such as Sjgrens syndrome and lupus. The

calculated specificity in any given study will be increased by exclusion of the confounding conditions

from the control group and decreased by the inclusion of older people or patients with SLE. Ideally we

would have accurate numbers reflecting the clinical context of each individual patient but that is,

obviously, impossible.

Taken lightly, sensitivity and specificity can be easily overvalued in practice. The clinician needs to

consider the limitations of these numbers. Let us consider, for example, ANA antibodies and the

diagnosis of systemic lupus.

It is certainly remarkable that ANA antibodies can be found in 95% of patients with systemic lupus. Anegative ANA test certainly makes the diagnosis of SLE very unlikely. A positive test supports the

diagnosis but the impact will depend on the clinical scenario. Positive ANA is also found in about 5%

of the general population. However, SLE is a rare disease, affecting approximately 1 in 2000 of the

population. This makes SLE a relatively rare cause of positive ANA. Admitting that all people with

musculoskeletal symptoms were blindly screened with ANA (approximately 20% of the total

population), 100 in 2000 of the population would be found to have ANA while only one would have

actual SLE. Most people with positive ANA test do not have SLE or actually any other rheumatic

condition. Similar limitations, obviously, apply to other tests.

Adequate weighing of sensitivity and specificity can be helped by stating to oneself the

complementary message: rheumatoid factor is present in 80% of patients with rheumatoid arthritis

(sensitivity) therefore 20% of patients with rheumatoid arthritis do not have rheumatoid factor.

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Specificity of ANA for lupus in a given study was 92%, therefore 8% of those without the disease had

positive ANA.

The adequate impact of test results on the probability of the diagnosis is better supported by

consideration of the pre-test probability and the likelihood ratio. These and other crucial aspects of

weighing evidence and lab results are explored in more depth in another module of this course,

dedicated to the critical appraisal of evidence.

KEY SUMMARY POINTS

Willing or not, all practicing clinicians follow strings of thought, maps of clinical reasoning:

being aware of your own, revising and ensuring its accuracy will make a crucial contribution to

your expertise and performance.

Reflect on your practice, take lessons from your experiences and incorporate them into your

mind map.

Focus on the typical characteristics of each condition and on the crucial aspects that

differentiate it from similar ones. Given great attention to sound indicators of prognosis, activity

and progress.

Never forget the absolutely decisive role of enquiry and examination in rheumatological

diagnosis.

Balance, as best you can, the need to guide your patient through the enquiry and his freedom

to express his concerns.

Always be critical about the clarity, validity, accuracy, sensitivity and specificity of clinical and

laboratory data you use.

Be aware of the importance of words as guides of thought: exercise the use of clinical

descriptors that are as accurate and precise as possible.

Make a problem representation in one sentence.

Consider the mind map we offer in this chapter as a mere example, waiting to be adapted

and continually revised by yourself, in search for the map that works best for you and your

patients.

diagnostic strategy in rheumatology

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