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7 Articles in Volume 4, Issue #5
A Case For Intractable Pain Centers: Part 1
Co-Existing Psychological Factors
Cold Lasers in Pain Management
Diagnosing Diffuse Aches and Pains
Occipital Nerve Block for Cervicogenic Headaches
Opioid Therapy in Chronic Non-cancer Pain Management
Reflex Sympathetic Dystrophy (RSD)

Diagnosing Diffuse Aches and Pains

A clinical approach to differentially diagnosing the patient who reports that “it hurts all over.”

Diffuse aches and pains, with features suggesting an origin in muscles, bones or joints, are symptoms that commonly bring patients to the family medicine practitioner. The practitioner has the responsibility to differentially diagnose from among the numerous diverse disorders that include such complaints, as well as identify those patients who have particularly serious underlying conditions and, therefore, will need referral for specialist investigations.

While it is clearly inappropriate to subject all such patients to elaborate, sometimes invasive, investigation, it is necessary to initiate a process of screening for likely conditions, using the history, physical examination, and simpler laboratory investigations. Once a diagnosis is suspected, the subsequent confirmatory investigations generally follow a standard pattern. The prize of early diagnosis depends more on the initial screening than the subsequent investigation, and is thus mainly in the hands of the general family medicine practitioner.

For those cases that seem to defy definitive diagnoses, the responsibilities of the physician are: first, to decide which cases warrant further investigation for serious underlying conditions; and, second, how to handle those in which there is no clear evidence of significant underlying disease. This article is concerned primarily with the first aspect. A conceptual approach that includes simple clinical and laboratory screening tests — and relies on a simplified flow chart to lead to the appropriate diagnostic considerations — is described in the following sections along with useful diagnostic pointers.

Early Pointers to a Likely Diagnosis

Figure 1 provides a listing of some of the more important conditions that can cause diffuse aches and pains, and is formatted as a simplified flow chart showing the early pointers to a likely diagnosis. An initial consideration involves the erythrocyte sedimentation rate (ESR), which is important in separating the inflammatory from the non - inflammatory disorders. It is a nonspecific test, but its familiarity and simplicity make it an invaluable screening test. A markedly elevated ESR may be the first pointer to a number of conditions, such as certain arthritic disorders, polymyalgia rheumatica, multiple myelomatosis, systemic lupus erythematosus, or secondary carcinomatosis. On the other hand, in the presence of a normal ESR, the serum alkaline phosphatase (SAP) level may yield important information. For example, the SAP level may be increased in both liver and metabolic bone diseases. Hence, the value of the SAP level as a screening test in the context of diffuse aches and pains with an elevated level pointing to the need to exclude conditions such as liver disease and osteomalacia, while normal SAP and normal ESR levels may point to other conditions to specifically consider in the differential diagnosis. After taking the history and examining the patient, the appropriate laboratory tests to request can then be considered. The conditions specified in Figure 1 will be considered briefly in turn, emphasizing the features that provide the most useful diagnostic pointers.

Inflammatory Polyarthritis

This includes rheumatoid arthritis as well as conditions such as ankylosing spondylitis and psoriatic arthritis. The most important clue in the history is the complaint of distressing early morning stiffness, lasting half an hour or sometimes much longer. Patients with ankylosing spondylitis are predominantly men in the third or fourth decade,1 may describe episodes of iritis or of painful heels (“plantar fasciitis” or Achilles tendonitis), or give a positive family history. Rheumatoid factor is tested negative.

In the case of ankylosing spondylitis, morning stiffness is an equally important early symptom, but the local signs of arthritis are too easily overlooked. Any reduction in spinal movements is significant, but the most useful tests are lumbar spinal flexion and lateral bending range of motion. Tenderness of the sacroiliac joints and reduced chest expansion (1

Physical examination in the early rheumatoid patient (most typically middle aged women) will show signs in peripheral joints involvement (especially in the hands and feet). These joints are tender on compression, swollen, painful on full movement with limited range of motion. A “polymyalgic” presentation of rheumatoid arthritis is rare, and the diagnosis is unlikely in the absence of local evidence of joint inflammation.3,4

Psoriatic arthritis appears in 5% of patients with psoriasis. Skin lesions are clear and there are characteristic X-ray findings. “Pencil-in-cup” deformity2 and sacroiliac joint involvement are common occurrences on X-ray.

“Secondary carcinomatosis can present with aches and pains as a result of skeletal deposits and can be much more difficult to diagnose at presentation.”

Figure 1. Early diagnostic pointers to the most common causes of diffuse aches and pains. Note: always consider human immunodeficiency virus (AIDS-related) disorders as well.

Screening Tests For Inflammatory Polyarthritis

If the history and/or signs raise a suspicion of inflammatory polyarthritis, then the routine laboratory screening tests are the ESR and the autoantibody tests for rheumatoid factors (latex test) and antinuclear antibodies (ANA). The latex test may be positive early in rheumatoid arthritis (approximately 80% of cases), while the ANA test is a test for systemic lupus erythematosus. A medication-induced lupus reaction should always be considered. X-rays of the pelvis and lumbar spine may be useful if ankylosing spondylitis is suspected, by revealing sacroiliitis and bamboo spine sign, but radiology is unlikely to be helpful in early rheumatoid arthritis. Similarly, tissue typing for human leukocyte antigen (HLA-B27) is not very useful as a screening test for ankylosing spondylitis.

Polymyalgia Rheumatica8

This is defined by the taxonomy of the International Association for the Study of Pain (IASP) as diffuse, aching pain, stiffness in the neck, shoulder or hip girdle, with a raised ESR, sometimes associated with giant cell vasculitis which is predominantly steroid responsive.6 This common and important condition must be excluded in all older patients complaining of diffuse aches and pains. Its importance lies in its frequent association with giant cell arteritis, which may lead to irreversible blindness. This can be prevented by appropriate corticosteroid treatment, but prevention requires diagnosis, which is easily overlooked, particularly in the very elderly. In a typical case, the patient will complain of distressing ‘muscular’ aches, particularly in a proximal (girdle) distribution, with severe, prolonged and incapacitating early morning stiffness.

The key screening test is the ESR, which will almost invariably be markedly elevated, sometimes over 100 mm/h (an unexpectedly normal result should be repeated). Some of these patients also have signs and symptoms of giant cell arteritis (such as an inflamed segment of a temporal artery and tenderness over the temporal artery), and most of them will require specialist investigation to exclude conditions that may mimic polymyalgia rheumatica (such as multiple myelomatosis). However, it is critical to recognize polymyalgia rheumatica as a possible diagnosis, and the important clues are girdle muscle pains, early morning stiffness, and an elevated ESR.

Myelomatosis And Secondary Carcinomatosis7,8

The only common primary neoplasm to present as diffuse aches and pains is multiple myelomatosis (although the more typical presentation is sudden onset of pain as a result of a compression fracture of the vertebra). Bone tenderness may be a clue to the diagnosis, but the important screening test is, again, the ESR. Most patients with myelomatosis have a markedly elevated ESR, often with anemia. This is an indication for more detailed investigations.

Secondary carcinomatosis can present with aches and pains as a result of skeletal deposits and can be much more difficult to diagnose at presentation. Screening tests such as the ESR and SAP measurements may be normal, and there may not be bone tenderness. Even awareness of the likely primary tumor sites (breast in women, prostate in older men, and bronchus in both sexes) may not prevent the diagnosis being missed. Radiology most often provides the eventual diagnosis. When bony secondaries are suspected, but the standard X-rays are normal, bone-seeking radioisotope scans may be useful.


Polymyositis is an inflammatory disease of skeletal muscles leading to muscle degeneration and weakness. In dermatomyositis this is accompanied by a characteristic skin rash. Both are rare causes of diffuse aches and pains. The constant physical sign, which should prevent the diagnosis being missed, is proximal (girdle) muscle weakness. This is best sought by asking the patient to lie flat on his or her back, fold the arms across the chest, and then rise to a sitting position while the examiner provides counter pressure downward on the knees. Muscles are often tender to palpation. Serum levels of muscle enzymes (creatinine kinase, aldolase) are elevated and muscle biopsy will confirm the diagnosis. An occult malignancy has been reported in 8% of cases in one series.

Metabolic And Other Bone Diseases9

A variety of non-neoplastic and non-infective diseases of bone may present as diffuse aches and pains. They are all caused by disorders in normal bone turnover. These include: (a) disorders due to failure of mineralization of normal osteoid tissue (osteopenia), such as osteoporosis, osteomalacia, and osteitis fibrosa (which may reflect hyperparathyroid bone disease or renal osteodystrophy); and (b) disorders due to increased matrix production and/or reduced resorption (osteosclerosis), such as in renal failure or hypoparathyroidism.17

Osteoporosis is the most common of these conditions (particularly in postmenopausal women), although, like multiple myeloma, it is more likely to present as localized pain as a result of a compression fracture of the vertebra (loss of height), rather than diffuse aches. Even though it is well known that postmenopausal women and patients on corticosteroid drugs are most at risk, diagnosis is complicated because a confident radiological diagnosis can be made only when the condition is well advanced. Also, there is no serum biochemical screening test, with normal serum calcium, inorganic phosphorus, and SAP values typically reported.

Paget’s disease, osteomalacia (common after gastric surgery in the United States), hyperparathyroid bone disease, and renal osteodystrophy may all cause diffuse aches and pains.15,17 However, because they all increase osteoblastic activity, they all cause an elevation of the SAP level, and this provides a useful screening test. It is only a screening test, however; since it does not differentiate among them, and liver disease may also elevate the level. (More elaborate tests allow differentiation between alkaline phosphatase from bone and from the liver, e.g., SAP electrophoresis or liver function test). The patient with diffuse pains and an elevated SAP level requires further tests to establish the cause. Paget’s disease (a common finding in older patients, but a rare cause of pain unless very extensive or involving a joint). Paget’s disease of bones can be identified on X-ray.

Osteomalacia is the accumulation of unmineralized bone with the association with low bone formation rate with decline in bone strength. This is an important cause of skeletal aches and muscle weakness in Asian immigrants, hypovitaminosis D, patients with malabsorption, after gastric bypass surgeries and the elderly. Osteomalacia is confirmed by typical radiological changes.15,17

Renal osteodystrophy (a metabolic bone disease that may accompany chronic renal failure) has features of both osteomalacia and hyperparathyroidism; subperiosteal erosions are usually present on radiology.

Hyperparathyroidism (Osteitis Fibrosa) is rare and associated with an elevated serum level of calcium. This is commonly due to parathyroid adenoma (primary hyperparathyroidism). Secondary hyperparathyroidism occurs due to renal or gastrointestinal pathology. The diagnosis is confirmed by high levels of fasting serum calcium and parathyroid hormone (PTH).17

Viral hepatitis can be associated with arthraligia and muscle pain. This occurs early in the disease but can persist if chronic hepatitis developes. Elevated liver enzymes and SAP, together with serological/viral tests,15 provide positive indicators for viral hepatitis.

Generalized Osteoarthritis9,17

Osteoarthritis is usually limited to one or two joints, but may occur in a generalized form. While osteoarthritis is a common cause of localized pains, it is over-diagnosed as a cause of widespread aches and pains. Before making such a diagnosis it is necessary to exclude other conditions by establishing that any morning stiffness lasts no more than a few minutes, and that the ESR and SAP levels are normal. On the positive side, it is necessary to remember that symptomatic osteoarthritis is normally associated with signs such as limitation and pain on maximum passive movement, night pain and early morning stiffness, as well as definite radiological changes. Heberdon’s nodes can be seen in primary osteoarthritis.

Degenerative disease of the spine is also over diagnosed as a cause of widespread aches and pains. From middle age, most people have radiological evidence of cervical and lumbar spondylosis, often gross, but this correlates poorly with symptoms. Here again, clinical and laboratory screening tests have to be applied to exclude other underlying disorders, while, on the positive side, active and passive maximum movements of the different spinal regions should reproduce the symptoms.


Vague skeletal pains may be a presenting complaint and clinical awareness is the only way to avoid missing the diagnosis. The family practitioner may be alerted to this by a complaint of cold intolerance, the typical facies, carpal tunnel syndrome, a characteristic delay in the relaxation phase on eliciting a tendon reflex, constipation, and disorder of the menstrual cycle.

“Paget’s disease, osteomalacia (common after gastric surgery in the United States), hyperparathyroid bone disease, and renal osteodystrophy may all cause diffuse aches and pains.”15,17

Fibromyalgia Syndrome (FMS)11,12,17,18

Until recently, fibromyalgia was not generally accepted as a specific medical condition, but rather as a ‘rag-bag’ diagnosis applied to unexplained muscular pains. This is a disorder disproportionately represented in women (approximately 90% in one series).11,12 The American College of Rheumatology (ACR) criteria include widespread pain (defined as pain above and below the waist; pain on both left and right sides of the body; and axial skeletal pain, involving cervical spine or anterior chest or thoracic spine or low back). There is decreased pain threshold and pain in at least 11 out of 18 specified tender points on digital palpation (with an approximate force of 4 kg). In addition, there may be complaints of headaches, insomnia, irritable bowel, fatigue, depression, and cognitive (e.g., attention/concentration and memory) dysfunctions. The syndrome may be “primary” (in which case standard investigations are negative) or “secondary” to some other rheumatic disorder, trauma, hypothyroidism, or other disease.

There is strong evidence for abnormal central pain processing in the central nervous system in FMS. Acute and repetitive tissue trauma with sensitization of the central nervous system (CNS) may play a role. This can lead to augmentation of nociceptive peripheral pain signals.15,17,18

Pain In HIV/Aids Disorders13,14,15,17

A wide range of painful syndromes can occur with HIV disorders. These include headache (e.g., due to CNS involvement by HIV infection, tumors or opportunistic infections), painful extremities (e.g., associated with peripheral neuropathies due to HIV antiviral therapy), rheumatological manifestations (arthritis and arthralgia) with sacroiliitis, and myopathies. Painful Articular Syndrome refers to a disorder seen in 10 % of HIV infected individuals and characterized by short duration of severe articular pain. History of intravenous drug abuse, blood transfusion, and/or sexual activities should give a clue. Pain is more common as the disease progresses. HIV test(s) should confirm the diagnosis.13,15,17

Non-Organic Pain Syndrome14,15,16

It is extremely difficult to attribute complaints of diffuse aches and pains entirely to psychological disorders (e.g., anxiety, depression, hysteria, etc.), even in the absence of other specific organic disease signs, physical examination findings, or laboratory screening tests. On the other hand, a much higher incidence of diffuse aches and pains are reported in association with psychological disorders. Depression is a particular case in point. However, attempts to identify a “pain-prone” personality and related concepts have been relatively unrewarding and the literature purporting to support such notions is substantially flawed methodologically. While there may be some instances in which psychological factors may be strongly or exclusively influencing complaints of bodily aches and pains, there is no definitive test for this. Such a determination requires diagnosing by exclusion and is a hazardous enterprise. A pain management mental health specialist (e.g., psychologist or psychiatrist) may be required to better assess the relative influence of psychological forces driving such complaints. Regardless, it is important to keep in mind that substantial numbers (e.g., 13% to 30% in the instance of “conversion” symptoms) initially diagnosed with a “psychogenic” disorder later develop diagnosable physical disorders that in retrospect would have included major aspects of the initial symptom manifestation. Moreover, improvements in complaints of aches and pains by means of psychopharmacologic treatment (e.g., antidepressant therapy) does not confirm a “psychogenic” diagnosis either, since such psychopharmacologic agents typically have multiple effects that may share overlapping modes of action (e.g., analgesic effects in addition to mood elevation and sleep induction).


Multiple aches and pains, a common clinical presentation, present a challenge in making a clinical diagnosis and require a logical step-by-step approach to the history as well as a series of screening investigations. The following are practical points to consider:

  • The most useful investigations are the erythrocyte sedimentation rate (ESR), serum alkaline phosphatase (SAP) level, rheumatoid factors (latex test), and antinuclear antibodies (ANA) if rheumatoid disease is suspected.
  • Inflammatory polyarthritis may present early as general non-specific aches, and stiffness that is at its worse in the morning.
  • Ankylosing spondylitis often has an early history of iritis and painful feet and heels. The spine should be checked for lumbar flexion and lateral bending.
  • Polymyalgia should be considered in elderly patients with morning upper girdle aches and pains and stiffness. The ESR is often over 100 mm/h.
  • Myelomatosis often has a sudden onset (as a result of a crushed vertebra); bone tenderness is a feature with a high ESR and is often accompanied by anemia.
  • Consider possible carcinomatosis as a cause even before a primary cause is apparent.
  • In polymyositis, upper girdle muscle weakness is a key sign.
  • Metabolic diseases to be considered are osteoporosis, osteomalacia (in elderly immigrants), Paget’s disease and hyperparathyroidism. SAP testing is helpful in differentially-diagnosing hyperparathyroidism and renal osteodystrophy since these conditions exhibit a increased SAP level.
  • Generalized osteoarthritis is not a common cause of aches and pains.
  • “Spondylosis,” “fibrositis,” and “psychogenic aches” are diagnoses fraught with danger and should only be considered after all other causes are ruled out. Further, if symptoms persist, such diagnoses should be revisited and more extensive investigations conducted.
  • Always consider the possibility of HIV related pain syndrome.
Last updated on: January 28, 2012
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