What conditions are associated with calcinosis?

Conditions Associated with Calcinosis

Calcinosis is most strongly associated with connective tissue diseases, particularly systemic sclerosis (especially the limited cutaneous form/CREST syndrome), dermatomyositis, and overlap syndromes. 1

Primary Connective Tissue Disease Associations

Systemic Sclerosis

• Most commonly seen in limited cutaneous systemic sclerosis (lcSSc), formerly known as CREST syndrome (Calcinosis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia) 1
• Affects approximately 25% of patients with systemic sclerosis 2
• Associated clinical features:
  • Longer disease duration
  • Digital ulcers
  • Acro-osteolysis
  • Positive anticentromere antibody
  • Positive anti-PM/Scl antibody 2

Dermatomyositis

• Common complication in juvenile dermatomyositis (JDM) 1
• Presence suggests active disease in JDM and delay in diagnosis and treatment 1
• Less common in adult dermatomyositis compared to JDM 1
• Can be found in dermatomyositis/scleroderma overlap syndrome 1

Other Connective Tissue Diseases

• Systemic lupus erythematosus 3
• Mixed connective tissue disease 3

Anatomical Distribution

Calcinosis can present in various anatomical locations:

• Subcutaneous tissues (most common) 1, 4
• Intramuscular 1, 4
• Fascial planes 1
• Areas prone to trauma (elbows, knees) 1
• Periarticular regions affecting nearly all joints 4
• Spinal and paraspinal areas (cervical and lumbar regions) 5

Clinical Implications

Calcinosis deposits can lead to significant morbidity:

• Pain and disability 3
• Muscle atrophy 3
• Joint contractures 3
• Skin ulceration 3
• Recurrent local inflammation 3
• Secondary infections 3
• Impaired quality of life 4

Pathophysiological Mechanisms

Several mechanisms have been proposed for the development of calcinosis:

• Local tissue trauma 6
• Chronic inflammation 6
• Vascular hypoxia 6
• Dysregulation of bone matrix proteins 2
• Dystrophic calcification in damaged or devitalized tissues (with normal calcium/phosphorus metabolism) 3

Diagnostic Approaches

Calcinosis can be diagnosed through:

• Clinical examination 2, 6
• Plain radiography 2, 6
• Experimental methods:
  • Ultrasonography 6
  • Multidetector computed tomography 6
  • Dual-energy computed tomography 6

Treatment Challenges

Treatment of calcinosis remains challenging with limited evidence for effective interventions:

• Pharmacological options with variable and modest results:
  • Diltiazem (may produce partial response) 1
  • Colchicine 1, 3
  • Bisphosphonates 1, 3
  • Probenecid 1, 3
  • Warfarin 1, 3
  • Minocycline 1, 3
  • Rituximab 1
  • Sodium thiosulfate 1
  • Treprostinil 1
  • Abatacept (case report) 1
• Surgical excision remains the mainstay of treatment for symptomatic lesions 4, 2
• Other approaches:
  • Carbon dioxide laser therapy 1, 3
  • Intralesional corticosteroids 1

Clinical Pitfalls and Caveats

• Calcinosis is often resistant to medical therapy, making management challenging 1
• Delayed diagnosis and treatment of underlying conditions (especially JDM) may increase risk of calcinosis 1
• Despite treatment, calcinosis may eventually regress but can leave complications such as joint contractures 1
• Surgical treatment should be considered for symptomatic lesions to improve quality of life when medical management fails 4
• Minimally invasive surgical approaches can be effective for spinal calcinosis 5

Understanding the associations of calcinosis with specific connective tissue diseases is crucial for early recognition, monitoring, and management of this challenging condition.