Practice Paper 4: Answers
Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar in Get ahead! Medicine, 2016
Systemic sclerosis is a connective tissue disorder characterized by thickening and fibrosis of the skin (scleroderma) with involvement of internal organs. There are two forms: a limited cutaneous type (60%) and a diffuse cutaneous type (40%). Limited cutaneous scleroderma is limited to the distal limbs (i.e. distal to the elbows and knees). Other features include a beaked nose and small, furrowed mouth (microstoma). Limited cutaneous scleroderma also encompasses the CREST syndrome, which is characterized by calcinosis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia. Calcinosis is the formation of calcium deposits in the soft tissues, often seen on the pulps of the fingers. Raynaud’s phenomenon is an idiopathic condition with episodic digital vasospasm precipitated by a cold environment, as a result of which the affected fingers or toes become white and may be painful. Oesophageal dysmotility is manifested as dysphagia and reflux. Sclerodactyly describes the presence of tight, shiny skin over the fingers, producing a fixed flexion deformity. In limited cutaneous scleroderma, the anticentromere antibody is characteristically positive. Pulmonary hypertension is a common internal manifestation.
Calcinosis Cutis
Charles Theisler in Adjuvant Medical Care, 2023
Calcinosis cutis is a condition where calcium salt crystals accumulate within the dermis (skin). Lesions usually appear as small, firm, white or yellow lumps (papules, plaques, or nodules) on the surface of the skin that may be hard or soft. A solitary lesion may develop, although multiple lesions are more common. Lesions may become tender and ulcerate, discharging a creamy chalk-like material consisting mainly of calcium phosphate with a small amount of calcium carbonate.1 Calcinosis usually has no symptoms but can be painful in some cases. Calcinosis cutis commonly occurs in patients with systemic sclerosis and dermatomyositis. There are four subtypes of this disorder. Any underlying cause (e.g., hypercalcemia and/or hyperphosphatemia) should be corrected.
Endocrine emergencies with skin manifestations
Biju Vasudevan, Rajesh Verma in Dermatological Emergencies, 2019
Skin manifestations are rarely seen in hyperparathyroidism. Calcinosis cutis due to elevated calcium and phosphate levels may be present. Calciphylaxis is a rare but life-threatening condition that is commonly associated with secondary hyperparathyroidism in the setting of chronic renal failure [16]. It is characterized by vascular calcification and thrombosis. It clinically presents with severe painful skin lesions (livedo reticularis, reticulate purpura, violaceous plaques, or indurated nodules) that evolve into nonhealing ulcers covered with black eschar and finally lead to tissue gangrene. Both the trunk and extremities can be involved [17].
Diagnosis and management of systemic sclerosis-related calcinosis
Published in Expert Review of Clinical Immunology, 2023
Michael Hughes, Ariane L Herrick
Calcinosis is common in patients with SSc, developing in approximately 20–40% [5–12]: the prevalence of calcinosis in any cohort of patients depends in part on how carefully it is looked for. Calcinosis occurs in both the limited cutaneous and diffuse cutaneous subtypes of SSc [6,12]. Most commonly it occurs around pressure points for example, in the fingers and hands (the thumb and index finger are most commonly affected [13–15]), and over the extensor aspects of the elbow, forearm, and knee. However, other areas can be involved, including the spine [16–18]. In some patients, calcinosis is subclinical, unrecognized by the patient and only noted on plain radiography. Conversely, in other patients calcinosis is the aspect of their disease with the largest impact on quality of life. This is because calcinosis can be very painful, disabling, and disfiguring and can ulcerate through skin (Figures 1 and 2), increasing the risk of the calcinosis becoming infected. Ulcers overlying areas of calcinosis can be particularly slow to heal [19], and one of the fears of patients with calcinosis is that the lesion(s) go on to ulcerate. A minority of patients develop very large lesions (‘pseudotumoral calcinosis’) [20]. Currently, there is no cure and so SSc-related calcinosis represents an area of major unmet clinical need [21].
Prevalence and clinical association with calcinosis cutis in early systemic sclerosis
Published in Modern Rheumatology, 2021
Chawiporn Muktabhant, Punthip Thammaroj, Prathana Chowchuen, Chingching Foocharoen
Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. The prevalence of calcinosis cutis in SSc ranges from 18 to 49% [5,6]. Calcinosis cutis occurs most frequently in the hands, followed by proximal upper extremities, knees or proximal lower extremities and hip, in order [5]. The pathophysiology of calcinosis cutis remains poorly understood. Chronic inflammation and vascular hypoxia are thought to play a role in the tissue damage that serves as a nidus for dystrophic calcification [7]. The other mechanisms include recurrent trauma and abnormalities in bone matrix proteins [5]. Common and potentially debilitating complications of calcinosis cutis include pain, local inflammation, ulceration, and infection [7]. Although diagnosis of calcinosis cutis is primarily performed by physical examination, radioimaging can help detection of subclinical deposits. Plain radiography is quite sensitive in detecting calcinosis cutis and is recommended as an initial imaging evaluation of calcinosis cutis [5,7].
Inflammatory myopathies: shedding light on promising agents and combination therapies in clinical trials
Published in Expert Opinion on Investigational Drugs, 2021
Rachel Zeng, Stefanie Glaubitz, Jens Schmidt
Calcinosis involves the deposition of carbonate apatite in soft tissue and is a severe and painful complication in autoimmune connective tissues diseases; in myositis syndromes it most commonly affects patients with DM or OM [3]. Various treatments of calcinosis have been proposed, but evidence is limited to case reports or retrospective case series. In a single-center retrospective cohort study of 16 myositis patients affected by calcinosis (11 DM, 4 OM, 1 PM), different calcinosis-specific treatments included diltiazem, bisphosphonates, warfarin, colchicine, IVIg, rituximab, infliximab, and sodium thiosulfate ointment, but none of these treatments showed sufficient effects on the reduction of calcinosis or the prevention of new sites involved [73]. Another single-center cohort study with 35 adult DM patients with calcinosis also showed no difference in treatment response between the bisphosphonate treatment group and the group not receiving bisphosphonate [74]. Regarding the use of rituximab, some case reports suggested beneficial effects, while others showed no improvement of calcinosis (summarized in [75]). There are recent reports on the successful use tofacitinib [76] or TNFα inhibitor [77] in myositis-associated calcinosis. In a retrospective case series involving the use of topical sodium thiosulfate in 28 patients with calcinosis cutis, 19 (68%) showed clinical improvement [78]. Currently, a prospective open-label study for the evaluation of efficacy and safety of intravenous sodium thiosulfate in DM patients with moderate to severe extensive calcinosis is ongoing [ClinicalTrials.gov Identifier: NCT03267277].
Related Knowledge Centers
- Calcification
- Calcinosis Cutis
- Calcium
- Hypercalcaemia
- Kidney Failure
- Metastatic Calcification
- Soft Tissue
- Dystrophic Calcification
- Milk-Alkali Syndrome
- Tumoral Calcinosis