Rheumatoid arthritis is a polyarthritis that results in symmetrical pain and swelling of the affected joints (also at rest). It particularly affects the metacarpophalangeal joints (MCPJs) and proximal interphalangeal joints (PIPJs), not the distal interphalangeal joints (DIPs).
Ulcerative colitis and IBD are associated with seronegative arthritides, not RA. The condition can also cause various extra-articular manifestations such as ocular symptoms, rheumatoid nodules and pulmonary fibrosis. Scleritis, episcleritis and keratoconjunctivitis sicca are more common than uveitis. Early intervention with disease-modifying antirheumatic drugs (DMARDs) plays a decisive role in successful treatment.

Adult onset Still’s disease (AOSD) is an uncommon systemic inflammatory disease on the clinical spectrum of autoinflammatory disorders. Its presentation and clinical course may result in several well-differentiated phenotypes: from a systemic and highly symptomatic pattern to a chronic articular pattern. Overproduction of numerous pro-inflammatory cytokines is observed in AOSD. Anakinra, a human interleukin (IL)-1R antagonist, has recently been approved in the treatment of AOSD. Denosumab is a RANK ligand inhibitor used in the treatment of osteoporosis. Mepolizumab is used in the treatment of severe asthma with elevated eosinophils. There is some evidence to support the use of tocilizumab, an anti-IL6 monoclonal antibody in adult onset Still’s, but there is stronger data favouring the use of tocilizumab in the treatment of rheumatoid arthritis. Rituximab is usually reserved for patients who are unresponsive to anakinra.

Arthritis mutilans is a rare (occurs in only 5% of the patients) and extremely severe form psoriatic arthritis characterized by resorption of bones and the consequent collapse of soft tissue. When this affects the hands, it can cause a phenomenon sometimes referred to as ‘telescoping fingers.’ The associated nail changes are also characteristic of arthritis.

Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless oedema, but oedema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule.

The patient most likely suffers from Paget’s disease of the bone as his radiological examination shows both osteolytic and osteosclerotic lesions. Any bone or bones can be affected, but Paget’s disease occurs most frequently in the pelvis > lumbar spine > femur > thoracic spine > sacrum > skull > tibia.

Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism.

Ankylosing spondylitis (spondylarthritis) is a chronic inflammatory disease of the axial skeleton that leads to partial or even complete fusion and rigidity of the spine. Males are disproportionately affected and upwards of 90% of patients are positive for the HLA-B27 genotype, which predisposes to the disease. The most characteristic early finding is pain and stiffness in the neck and lower back, caused by inflammation of the vertebral column and the sacroiliac joints. The pain typically improves with activity and is especially prominent at night. Other articular findings include tenderness to percussion and displacement of the sacroiliac joints (Mennell’s sign), as well as limited spine mobility, which can progress to restrictive pulmonary disease.
The most common extra-articular manifestation is acute, unilateral anterior uveitis. Diagnosis is primarily based on symptoms and x-ray of the sacroiliac joints, with HLA-B27 testing and MRI reserved for inconclusive cases. There is no curative treatment, but regular physiotherapy can slow progression of the disease. Additionally, NSAIDs and/or tumour necrosis factor-α inhibitors may improve symptoms. In severe cases, surgery may be considered to improve quality of life. The spine adopts a bamboo shape, not lordosis. The pain usually improves as the day progresses. leg raise test causes pain in cases of meningitis etc not in this case.

Reactive arthritis, (formerly known as Reiter’s syndrome), is an autoimmune condition that occurs after a bacterial infection of the gastrointestinal or urinary tract. It is categorized as a seronegative spondylarthritis because of its association with HLA-B27. Reactive arthritis primarily affects young men and usually presents with musculoskeletal or extra‑articular symptoms. The characteristic triad consists of arthritis, conjunctivitis, and urethritis. The diagnosis is based on clinical features such as patient history and physical examination; there are no specific tests for reactive arthritis. Treatment is primarily symptomatic and consists of the administration of NSAIDs, as most patients recover spontaneously. extraarticular dermatologic manifestations include skin lesions of the glans resembling psoriasis (balanitis circinata); hyperkeratinisation of the palms and soles (keratoderma blenorrhagicum), oral ulcers. There usually is no rash and the diagnosis is unrelated to the presence of rheumatoid factor. This is a clinical diagnosis.

Lateral epicondylitis (tennis elbow) is an overuse injury of the hand and finger extensor tendons that originate in the lateral humeral epicondyle that occurs following repeated or excessive pronation/supination and extension of the wrist (e.g., in racquet sports). Clinical features include pain and tenderness over the lateral epicondyle and along extensor muscles, thickening of the tendons. The examiner holds the patient’s hand with the thumb placed over the lateral epicondyle – The patient makes a fist, supinates the forearm, deviates radially, and extends the fist against the examiner’s resistance which results in pain over the lateral epicondyle. Conservative treatment includes rest, physiotherapy and orthotic braces. If this fails corticosteroids and lidocaine injections are employed. Surgery is indicated in patients with persistent symptoms despite 6 months of conservative treatment. Excision of abnormal tendon tissue; longitudinal incisions (tenotomies) in scarred and fibrotic areas to promote healing.

Felty syndrome is a severe subtype of seropositive Rheumatoid arthritis. Clinical triad consists of arthritis, splenomegaly, and neutropenia (leads to an increased risk of recurrent bacterial infections). Other symptoms include skin ulcers of the lower limbs (indicating vasculitis), hepatomegaly, fever, and chest pain (indicating pleuritis or pericarditis). It is associated with increased risk of developing non-Hodgkin lymphoma.

Temporal arteritis is a chronic large- and medium-sized vessel vasculitis that typically involves the temporal arteries. Classical symptoms include temporal headaches, jaw claudication, amaurosis fugax. Physical exam shows scalp tenderness, palpation of the temporal area may demonstrate an absent pulse, knot-like swelling and vision loss. Lab results reveal an increased erythematous sedimentation rate and C-reactive protein. Temporal artery biopsy confirms the diagnosis. Management approach: high-dose systemic corticosteroids should be promptly administered even before the diagnosis is established. Temporal artery biopsy confirms the diagnosis. Inability to manage this or administer glucocorticoids might lead to development of blindness.

Bilateral erosions of the sacroiliac joints on pelvic radiographs of patients with ankylosing spondylitis are an important feature of the modified New York classification criteria. Although HLA-B27 is commonly associated with AS, it can also be found in normal individuals. Back stiffness is worse in the morning and gets better as the day progresses. Tenderness and limited lumbar motion can be associated with other spine problems as well and is not characteristic of rheumatoid arthritis.

Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease as the anti-Ro and anti-La antibodies cross the placenta and lead to various life threatening complications. Studies show a high incidence of poor fetal outcomes for these patients. Congenital heart block, neonatal lupus, congestive cardiac failure, hydrops fetalis can all be caused as a result of Sjogren syndrome.

Behçet disease is a rare vasculitic disorder that is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. The systemic manifestations can be variable. Ocular disease has the greatest morbidity, followed by vascular disease generally from active vasculitis. Cutaneous manifestations can occur in up 75% of patients with Behcet disease and can range from acneiform lesions, to nodules and erythema nodosum. GI manifestations can be severe. Differentiating Behçet disease from active inflammatory bowel disease can be clinically difficult. Herpes would have ideally responded to acyclovir. Sarcoidosis does not have genital and oral ulcerations.

Polymyositis is an inflammatory disorder causing symmetrical, proximal muscle weakness. It is thought to be a T-cell mediated cytotoxic process directed against muscle fibres. It may be idiopathic or associated with connective tissue disorders. It may also be associated with malignancy for example small cell lung carcinoma.
Dermatomyositis is a variant of the disease where skin manifestations are prominent, for example a purple (heliotrope) rash on the cheeks and eyelids.
It typically affects middle-aged, female: male 3:1. Features include proximal muscle weakness +/- tenderness, Raynaud’s phenomenon, respiratory muscle weakness, interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia, dysphagia, dysphonia. Investigations: elevated creatine kinase, other muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) are also elevated in 85-95% of patients, EMG, muscle biopsy. Anti-Jo-1 antibodies are seen in pattern of disease associated with lung involvement, Raynaud’s and fever. Interstitial lung disease plays a major role in morbidity and mortality in patients with polymyositis and is considered a major risk factor for premature death in patients with myositis.

A variety of proteins compose the structure of microfibrils, the most prominent of which are the two fibrillins. Fibrillin-1 a scaffolding protein is encoded by FBN1 on human chromosome 15q21 and fibrillin-2 is encoded by FBN2 on 5q23. Mutations in FBN1 produce Marfan syndrome, a pleiotropic autosomal dominant connective tissue disorder with prominent manifestations in the skeleton, eye and cardiovascular system. A number of conditions related to Marfan syndrome are also due to FBN1 mutations.

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Arthrocentesis should be performed, especially in acute cases.
Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals.
Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils.
X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis).
Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. The other factors that are mentioned do not play a key prognostic role.

An overall concordance rate in monozygotic twins was documented to be 25% as compared to dizygotic twins with 3%. First degree relatives have a chance of around 3% of developing the disease. Caucasians show an increase frequency of HLA-B8. The Japanese lupus patients had a stronger association with HLA-DR2.

Pseudogout is a paroxysmal joint inflammation due to calcium pyrophosphate crystal deposition (calcium pyrophosphate dihydrate). Aetiology includes mostly idiopathic (primary form) and secondary form occurring as a result of joint trauma, familial chondrocalcinosis, hyperparathyroidism, hemochromatosis, gout, hypophosphatemia. Clinical presentation: Often asymptomatic.
Acute (pseudogout attack): monoarthritis (rarely oligoarthritis), mostly affecting the knees and other large joints (e.g., hips, wrists, and ankles). It may become chronic (can affect multiple joints). Osteoarthritis with CPPD (most common form of symptomatic CPPD): progressive joint degeneration with episodes of acute inflammatory arthritis typical of pseudogout attacks. Arthrocentesis should be performed, especially in acute cases. Polarized light microscopy: detection of rhomboid-shaped, positively birefringent CPPD crystals. Synovial fluid findings: 10,000-50,000 WBCs/μL with > 90% neutrophils. X-ray findings: cartilage calcification of the affected joint (chondrocalcinosis). Fibrocartilage (meniscus, annulus fibrosus of intervertebral disc) and hyaline cartilage (joint cartilage) may be affected.

A high level of anti-dsDNA in the blood is strongly associated with lupus and is often significantly increased during or just prior to a flare-up. When the anti-dsDNA is positive and the person tested has other clinical signs and symptoms associated with lupus, it means that the person tested likely has lupus. This is especially true if an anti-Sm test is also positive.

In the evaluation of someone with lupus nephritis, a high level (titre) of anti-dsDNA is generally associated with ongoing inflammation and damage to the kidneys.

A very low level of anti-dsDNA is considered negative but does not exclude a diagnosis of lupus. Only about 65-85% of those with lupus will have anti-dsDNA.

Low to moderate levels of the autoantibody may be seen with other autoimmune disorders, such as Sjögren syndrome and mixed connective tissue disease (MCTD).

Patients with disseminated gonococcal arthritis may present with dermatitis-arthritis syndrome (60%) of with localized septic arthritis. (40%). Arthritis-dermatitis syndrome includes the classic triad of dermatitis, tenosynovitis, and migratory polyarthritis. Gout usually involves a singe joint and does not cause vesicopustular skin rash. Reactive arthritis has ocular symptoms (conjunctivitis), urethritis, and arthritis. Fungal arthritis occurs rarely and it may occur after a surgical infection or fungal spread hematogenously. it presents with tender, red, hot and swollen joint with loss of range of motion.

To confirm the diagnosis, especially in patients with negative anti-Ro or anti-La antibodies, labial gland biopsy is done. In performing a labial biopsy, the surgeon typically makes a shallow 1/2 inch wide incision on either side of the inner lip after numbing the area with a local anaesthetic. Schirmer’s test determines whether the eye produces enough tears to keep it moist. This test can be done for ocular symptoms of Sjogren syndrome but is of no diagnostic importance as it can be positive with many other diseases.

Osteomalacia is a condition due to defective mineralization of osteoid. Occurs as a result of Vitamin D deficiency secondary to poor dietary intake and sun exposure, malabsorption e.g., inflammatory bowel disease and gastrointestinal bypass surgery. Radiological findings include reduced bone mineral density (a non specific finding), inability to radiologically distinguish vertebral body trabeculae (the film appears poor quality), looser pseudo fractures, fissures, or narrow radiolucent lines (these are the characteristic findings). Osteolytic or punched out lesions may be seen with multiple myeloma and bony metastases. Areas of sclerosis may be observed with conditions like osteosclerosis and Paget disease. A Brodie abscess is a subacute osteomyelitis, which may persist for years before progressing to a chronic, frank osteomyelitis.

Old age, persistent backache, weight loss, and osteosclerotic lesions make prostatic adenocarcinoma the most likely diagnosis. The sequelae include severe pain, pathological fractures, hypercalcemia and cord compression. Prostatic adenocarcinoma is detected by elevated levels of prostate specific antigen. Positive serology for borrelia burgdorferi would hint at Lyme disease which does not cause osteosclerotic bone lesions, neither would Neisseria gonorrhoeae have such a presentation.

A typical attack may last less than an hour but can also persist for longer. In primary Raynaud’s, attacks are more likely symmetric, episodic, and without evidence of peripheral vascular disease. Patients more commonly have a negative ANA and normal inflammatory markers. There should be no evidence of tissue gangrene, digital pitting, or tissue injury in primary Raynaud’s. In contrast, patients with secondary Raynaud’s will describe attacks that are more frequent, painful, often asymmetric and may lead to digital ulcerations.

Paget’s accelerates the remodelling process with old bone breaking down more quickly which disrupts the normal growth process. New bone development eventually adjusts to the faster pace and speeds up on its own. The pace is too fast for healthy bone growth, and the regrowth ends up softer and weaker than normal. The effect of this accelerated process causes bone pain, fractures, and deformities. Since osteosarcoma is a type of bone cancer linked to abnormal bone growth, this makes it a rare but possible complication of Paget’s disease although the chances of developing osteosarcoma are minimal. Fractures are painful and restrict movement whereas this patients pain is gradually developing. Pain associated with osteoarthritis is usually mild to moderate and worsens as the day progresses.

Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients. ANA are also found in 95% of the patients with SLE but they may also occur with other conditions like Juvenile inflammatory arthritis, chronic activity hepatitis, and Sjogren’s syndrome. Anti-Ro, although also found with SLE are more characteristic of Sjogren Syndrome. RF is usually associated with rheumatoid arthritis and cANCA with Wegener’s granulomatosis, Churg Strauss, and microscopic polyangiitis.

Osteoblastic (or sclerotic) bone metastases, characterized by deposition of new bone, present in prostate cancer, carcinoid, small cell lung cancer, Hodgkin lymphoma or medulloblastoma.

Pneumocystis carinii pneumonia, is an opportunistic fungal lung infection occurring almost exclusively in immunocompromised individuals. In 50% of cases, PCP is the first manifestation of AIDS (acquired immune deficiency syndrome), but it may be caused by other immunodeficiency disorders. PCP should be suspected in patients with a history of progressive dyspnoea and a dry cough with resistance to standard antibiotic treatment. Signs that support this diagnosis include a CD4 count < 200/μL, an increased beta-D-glucan level, and diffuse bilateral infiltrates on chest x-ray. Management of PCP includes high-dose trimethoprim/sulfamethoxazole (TMP/SMX), treatment of the underlying immunodeficiency disorder, and steroids in the case of severe respiratory insufficiency. TB is less likely to be present in this case as ESR is relatively low and chest x-ray appeared normal.