An elderly male presenting with non-deforming, symmetrical, inflammation of large joints and proximal muscle weakness in lower limbs, dry eyes and urticarial rashes

Case discussion

The summary of the clinical features and investigation of the case is given in table 01.

Table 1: Summary of the clinical features and investigation

The probable diagnosis could be:

1. Osteoarthritis (OA) or degenerative arthritis
2. Seronegative spondyloarthropathy (SSA)
3. Inflammatory myopathy either drug-induced or primary
4. Connective tissue disease (CTD) - Sjogren's syndrome (SS)
5. Sarcoidosis
6. Malignancy

Yes- support possibility No-against the possibility, Not- contributory, Yes/no- both are possible

Discussion 01

In elderly male patients with non-inflammatory backache and lower limb joint pain, the possibility of OA should be considered. Although the possibility of SSA is higher, as the patient had dandruff, the age does not favor the diagnosis. The presence of dry eyes could be considered part of aging. Since arthritis is present in conjunction with dry eyes, it is significant to consider the possibilities of sarcoidosis and Sjogren's syndrome. The occurrence of urticarial rashes can be considered a part of CTD and underlying malignancy. Elevated ALT and AST, in the absence of elevated ALP and GGT, suggest the possible source of these enzymes to be muscle. With proximal muscle weakness and a history of dry eyes, the physician can consider the possibility of CTD with myopathy or drug-induced polymyositis, since the patient is on atorvastatin. The presence of dry eyes and lower limb arthritis can be seen as associated with sarcoidosis. The proximal myopathy is also well described with sarcoidosis. Elderly patients with unexplainable proximal myopathy, back pain, and arthritis Para neoplastic syndrome should be excluded. However, four years is a longer duration for occurring malignancy-associated syndromes. X-ray of the chest was normal and the pelvis showed degenerative changes.

Considering the above possibilities, further investigations were performed, and the results are given below:

Creatine phosphokinase (CPK)- 1650 IU/dl, Serum Vit D3- 20 IU/dl, angiotensin-converting enzyme (ACE) - 50 IU/ dl (> 52), serum B12- 235 IU/dl, and positive myositis-specific antibodies (Mi – 2, Ku, PM – Scl, Jo-1, PL – 7, PL – 12, Ro-52).EMG showed myopathy features.

Final Diagnosis

Further investigations confirm the final diagnosis of inflammatory myositis (Ro 52 associated) with OA. This syndrome explains the presence of dry eye syndrome. However, the chances of drug-induced myopathy should be considered until proven otherwise. Subsequently, atorvastatin was discontinued, and the patient was observed for 3 months there was no improvement in the enzyme concentration as well as muscle weakness. Hence the final diagnosis could be concluded as SS with inflammatory myositis (Ro52-associated) and OA.

Discussion 02 – The diagnosis of the case by criteria method

Approach by classification Criteria

In this section, I have attempted to discuss based on the existing and available criteria to conclude the diagnoses which were considered. For the diagnosis of Sarcoidosis currently, there are no well-accepted criteria. The criteria fulfilled by the present case are highlighted in the text

Classification Criteria for Polymyositis and Dermatomyositis

1. Skin lesions

• Heliotrope: red-purple edematous erythema on the upper palpebra
• Gottron's sign: red-purple keratotic, atrophic erythema or macules on the extensor surface of finger joints
• Erythema on the extensor surface of extremity joints, slight raised red-purple erythema over elbows or knees

2. Proximal muscle weakness (upper or lower extremity and trunk)
3. Elevated serum creatine kinase or aldolase level
4. Muscle pain on grasping or spontaneous pain
5. Myogenic changes on electromyography (short duration, polyphasic motor unit potentials with spontaneous fibrillation potentials)
6. Positive anti-Jo-1 antibody test (histidyl-tRNA synthetase)
7. Non-destructive arthritis or arthralgias
8. Systemic inflammatory signs (temperature: more than 37°C [98.6°F] at the axilla, elevated serum C-reactive protein level, or accelerated erythrocyte sedimentation rate of more than 20 mm per hour by Westergren)
9. Pathologic findings compatible with inflammatory myositis (inflammatory infiltration of skeletal evidence of active regeneration may be seen)

Patients presenting with at least one finding from item 1 and four findings from items 2 through 9 are said to have dermatomyositis (sensitivity, 94.1 percent, and specificity of skin lesions against systemic lupus erythema and systemic sclerosis, 90.3 percent). Patients presenting with at least four findings from items 2 through 9 are said to have polymyositis (sensitivity, 98.9 percent, and specificity of polymyositis and dermatomyositis against all control diseases combined, 95.2 percent)

ESSG criteria for diagnosis of spondyloarthropathy.

For a patient to be classified as having SpA, he or she must satisfy one of two entry criteria: Inflammatory spinal pain OR synovitis that is either asymmetric or predominantly in the lower limbs.

Inflammatory back pain:

Back pain is considered inflammatory if four of the following five criteria are found:

The onset of back discomfort before the age of 40 years

Insidious onset

Persistence for at least three months

Associated with morning stiffness

Improvement with exercise

Asymmetrical synovitis: Asymmetrical synovitis, predominantly of the lower limbs is manifested by soft tissue swelling, warmth over a joint, joint effusion, and reductions in both active and passive range of motion, the symptoms are worse after a period of rest.

Additional criteria:

If a patient has one or both entry criteria listed above, he or she should then be evaluated for the presence of one or more of the following features:

Positive family history

Psoriasis?

Inflammatory bowel disease

Urethritis, cervicitis, or acute diarrhea within one month before arthritis

Buttock pain alternating between buttocks

Enthesopathy

Plain film radiographic evidence of sacroiliitis

Importantly, blood tests, including an assessment for the presence of HLA-B27, are not part of the ESSG criteria; in addition, only the sacroiliac joints need to be evaluated radiographically.

Sjogren’s syndrome

1. Ocular symptoms: a positive response to at least one of the following questions:
2. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
3. Do you have a recurrent sensation of sand or gravel in the eyes?
4. Do you use tear substitutes more than 3 times a day?
5. Oral symptoms: a positive response to at least one of the following questions:
6. Have you had a daily feeling of dry mouth for more than 3 months?
7. Have you had recurrently or persistently swollen salivary glands as an adult?
8. Do you frequently drink liquids to aid in swallowing dry food?

• Ocular signs-that is, objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:

1. Schirmer's I test, performed without anesthesia (</=5 mm in 5 minutes)
2. Rose bengal score or another ocular dye score (>/=4 according to van Bijsterveld's scoring system)
3. Histopathology: In minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score >/=1, defined as several lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4 mm²of glandular tissue
4. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:
5. Unstimulated whole salivary flow (</=1.5 ml in 15 minutes)
6. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary, or destructive pattern), without evidence of obstruction in the major ducts
7. Salivary scintigraphy showing delayed uptake, reduced concentration, and/or delayed excretion of tracer
8. Autoantibodies: presence in the serum of the following autoantibodies:
9. Antibodies to Ro (SSA) or La (SSB) antigens, or both

Revised Rules for Classification

For primary SS

In patients without any potentially associated disease, primary SS may be defined as follows:

1. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV (Histopathology) or VI (Serology) is positive
2. The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI)
3. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in the clinical-epidemiological survey

Sarcoidosis there are no accepted criteria

There are no specific criteria. The diagnosis is evidence of a non-infectious granulomatous lesion, with clinical features consistent with Sarcoidosis.

• Polyarthritis predominantly lower limb
• Erythema nodusam and other skin lesions
• Lymphadenopathy including hilar lymph nodes.
• Proximal myopathy
• Granulomatous iridocyclitis and dry eye
• Dry eye
• Pulmonary lesions.

Osteoarthritis. (Altman, R, et al.: Arthritis Rheum 34:505, 1991)

They are for individual joints as per ACR criteria. (ref for individual joint criteria http://www.rheumatology.org/Practice/Clinical/Classification/Classification_Criteria_for_Other_Diseases/)

The common denominators of all criteria are (The general aspect of these criteria is summarised and presented for interpretation purpose since the patient clinically appear to have hip and knee disease)

• Pain in the respective joints.
• Age above 50 years
• Stiffness less than 30 mins
• Low ESR and
• RF < 1:40
• Presence of crepitus and absence of signs of inflammation.

If go by criteria patient fulfills the criteria of OA, PM, SSA, and possible Sarcoidosis. However clinical discretion will help to consider the diagnosis of drug-induced Polymyositis and OA. However, in our follow-up, the patient made no recovery after drug withdrawal and the presence of Ro 52 suggests a possible Idiopathic Inflammatory Polymyositis.

The approach to a diagnosis thus should be based on a combined approach of clinical judgment based on existing criteria and the clinical circumstances including the circumstances of the development of the disease.

For instance, in the given circumstances the patient fulfills the criteria of SSA but for age. This was one of the commonest diagnoses considered by the participating discussant. The reason ascertained was lower limb arthritis and back pain. But the critical factor ignored in making that diagnosis was the age of the patient and the normal inflammatory pattern. Except for one discussant none considered OA. Probably biased since the patient is discussed in a special forum. Whatever the circumstances and the possible history of proximal muscle weakness, the commonest possibility in an elderly gentleman with lower limb arthritis and non-inflammatory back pain should be degenerative arthritis- OA.

We did see apart from one or two discussants; they paid attention to elevated SGOT and SGPT without elevated GGT and suggested performing CPK. The drug-induced myopathy was considered an important possibility. Dry eye was not given adequate importance by many of the discussants. If one puts all together Ro 52 positive Sjogrens syndrome where the dry eye, proximal myopathy, and arthritis can be explained. The patient being on long-term statins it is reasonable to conclude the first diagnosis as Drug-induced myopathy and to follow up with the patient for a few more months for improvement in the symptoms. No such improvement was noted in the present patient, and the improvement was noticed only after initiating steroids.

References:

1. Tanimoto K, Nakano K, Kano S, Mori S, Ueki H, Nishitani H, Sato T, Kiuchi T, Ohashi Y. Classification criteria for polymyositis and dermatomyositis. J Rheumatol. 1995 Apr;22(4):668-74.
2. Sweiss NJ, Patterson K, Sawaqed R, Jabbar U, Korsten P, Hogarth K, Wollman R, Garcia JG, Niewold TB, Baughman RP. Semin Respir Crit Care Med.2010 Aug;31(4):463-73. doi: 10.1055/s-0030-1262214. Epub 2010 Jul 27.