PRACTICE DEVELOPMENT Understanding calcinosis and calciphylaxis KEY WORDS Calcinosis cutis is a rare cause of non-healing leg ulceration. There are many factors Calcinosis cutis that can delay the healing of venous leg ulceration and the deposition of calcium in Calciphylaxis the skin known as calcinosis cutis is one of these factors. There are five distinct forms: Warfarin-induced skin dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic necrosis calcification and calciphylaxis. Warfarin skin necrosis has common clinical features with calciphylaxis and is therefore included in this article, which describes the types of calcinosis cutis, their clinical presentations and limited treatment options. The aim is to highlight these unusual causes and to assist healthcare professionals when faced with a non-healing ulcer. eg ulceration can be defined as a defect in neurotransmission and the blood coagulation the dermis located on the leg (Franks et al, pathway. At a cellular level, it is implicated in 2016). Leg ulceration is a significant clinical cell-to-cell communication (Walshe and Fairley, Lproblem with the majority attributing venous 1995). In the skin, it is specifically concerned with hypertension as the underlying disease process with keratinocyte proliferation, differentiation and venous leg ulceration affecting 1% of the population adhesion (Smith and Yamada, 2002). in the western world (Posnett et al, 2009). However, The level of serum calcium is closely there is a multitude of causative factors of leg ulcers, controlled by the parathyroid hormone. with the term leg ulcer purely signifying the clinical Regardless of this regulation, it is possible for manifestation and not the underlying aetiology. calcium salts and minerals to be deposited in In certain situations, despite confidence in cutaneous and subcutaneous tissue (Walshe and the diagnosis, the leg ulcer fails to respond to Fairley, 1995; Kupitz et al, 2007). appropriate treatment and make the expected Calcification is an acquired disorder in which progression. Under these circumstances, the there is deposition of insoluble calcium in healthcare professional should revisit the cutaneous tissue. Large amorphic deposits might assessment process to establish if there is also be found in subcutaneous tissue (calcinosis an alternative diagnosis that may have been cutis), and in mural calcification calcium can be overlooked (Franks et al, 2016). Calcinosis and found within the walls of the arteries (Pugashetti calciphylaxis are rare causes of delayed healing in et al, 2011). individuals with leg ulceration. There are four types of calcinosis cutis: dystrophic calcification, metastatic calcification, CALCIUM idiopathic and iatrogenic calcification with Most calcium in the human body is in a relatively calciphylaxis now added as the fifth variant insoluble form. It is the primary mineral in (Reiter et al, 2011a) (Table 1). the bony skeleton and is also found in teeth. TRUDIE YOUNG The remainder is found in a soluble form in DYSTROPHIC CALCIFICATION Director of Education and the intracellular and extracellular space, e.g. Dystrophic calcification (DC) is the most common Training, Welsh Wound Innovation Centre, Ynysmaerdy, cytoplasm. Calcium is involved in skeletal type of calcinosis cutis, although it can also occur Rhondda Cynon Taff, Wales muscle and myocardial contraction as well as in muscles and tendons (Smith and Yamada, 2002; 40 Wounds UK | Vol 14 | No 3 | 2018 Table 1. Types of calcification PRACTICE DEVELOPMENT Type of Trigger Diagnostic Levels of serum Associated Internal Physiological Common sites Clinical presentation Specific treatment calcinosis assessment calcium/phosphate conditions organs presentation cutis affected Dystrophic Tissue trauma and X-ray, analysis of Normal CREST Syndrome, No Multiple and local Leg ulcers, injection sites, Presence of hard calcium Removal of calcium structural damage calcium deposits Systemic Lupus deposits of calcium non-viable tissue, fingers, grainy deposits in the deposits to the skin once removed Erythematosus, elbows, forearms wound bed, chalky in the wound bed from the wound Panniculitis, Ehlers- exudate bed Danlos syndrome Metastatic Hypercalcaemia Haematological Abnormal Chronic kidney Kidney, Multiple and local Subcutaneous and deep Depending on the area Stabilisation of calcium and and/or investigation, x-ray disease lungs deposits of calcium tissue, e.g. gastric mucosa, affected phosphate levels, alteration hyperphosphatemia, arteries and veins in method of renal dialysis Idiopathic Unknown X-ray Normal Familial forms No Calcification of Localised, scrotum, Nodules under the No specific present and seen subcutaneous tissue around major joints, head, surface of the skin recommendations in infants extremities Iatrogenic Intravenous infusion Clinical Normal None No Elevated tissue Local to intravenous Calcium deposits at the Resite the intravenous of calcium chloride presentation concentration of infusion site site of the extravasation infusion and/or calcium calcium at the injury gluconate extravasation site Calciphylaxis Renal Tissue biopsy, Abnormal or normal Obesity, female Potential Calcium deposits Areas with an increase Mottled skin (retiform Parathyroidectomy if transplantation, end X-ray in the presence of gender, diabetes in skin, small and in subcutaneous fat, e.g. purpura), purple blood hyperparathyroid disease, stage renal disease hypercoagulability mellitus, medium sized blood abdomen, buttocks, thighs, blisters, nodules, skin wound debridement states secondary hyper- vessels producing clot lower legs and feet with the necrosis, ulcers with a and removal of calcium parathyroidism and formation within the latter two sites producing violaceous edge deposits, Warfarin medication vessels less severe clinical outcomes Treatment systemically and locally if infection/sepsis occurs. In renal failure alter method of dialysis to one with a lower calcium concentration Warfarin Commenced Skin biopsy Normal Female, obesity No Microthrombi Areas with an increase Paraesthesia, oedema, Alternate form of induced skin warfarin as an in dermal and in subcutaneous fat, e.g. mild rash, skin necrosis anticoagulation, wound necrosis anticoagulant subcutaneous tissue, abdomen, buttocks, legs, debridement therapy within the venules and deep thighs, mammary tissue preceding 24–48 veins, endothelial cell hours damage, red blood cell extravasation Table 1. Types of calcification Type of Trigger Diagnostic Levels of serum Associated Internal Physiological Common sites Clinical presentation Specific treatment calcinosis assessment calcium/phosphate conditions organs presentation cutis affected Dystrophic Tissue trauma and X-ray, analysis of Normal CREST Syndrome, No Multiple and local Leg ulcers, injection sites, Presence of hard calcium Removal of calcium structural damage calcium deposits Systemic Lupus deposits of calcium non-viable tissue, fingers, grainy deposits in the deposits to the skin once removed Erythematosus, elbows, forearms wound bed, chalky in the wound bed from the wound Panniculitis, Ehlers- exudate bed Danlos syndrome Metastatic Hypercalcaemia Haematological Abnormal Chronic kidney Kidney, Multiple and local Subcutaneous and deep Depending on the area Stabilisation of calcium and and/or investigation, x-ray disease lungs deposits of calcium tissue, e.g. gastric mucosa, affected phosphate levels, alteration hyperphosphatemia, arteries and veins in method of renal dialysis Idiopathic Unknown X-ray Normal Familial forms No Calcification of Localised, scrotum, Nodules under the No specific present and seen subcutaneous tissue around major joints, head, surface of the skin recommendations in infants extremities Iatrogenic Intravenous infusion Clinical Normal None No Elevated tissue Local to intravenous Calcium deposits at the Resite the intravenous of calcium chloride presentation concentration of infusion site site of the extravasation infusion and/or calcium calcium at the injury gluconate extravasation site Calciphylaxis Renal Tissue biopsy, Abnormal or normal Obesity, female Potential Calcium deposits Areas with an increase Mottled skin (retiform Parathyroidectomy if transplantation, end X-ray in the presence of gender, diabetes in skin, small and in subcutaneous fat, e.g. purpura), purple blood hyperparathyroid disease, stage renal disease hypercoagulability mellitus, medium sized blood abdomen, buttocks, thighs, blisters, nodules, skin wound debridement states secondary hyper- vessels producing clot lower legs and feet with the necrosis, ulcers with a and removal of calcium parathyroidism and formation within the latter two sites producing violaceous edge deposits, Warfarin medication vessels less severe clinical outcomes Treatment systemically and locally if infection/sepsis occurs. In renal failure alter method of dialysis to one with a lower calcium concentration Warfarin Commenced Skin biopsy Normal Female, obesity No Microthrombi Areas with an increase Paraesthesia, oedema, Alternate form of induced skin warfarin as an in dermal and in subcutaneous fat, e.g. mild rash, skin necrosis anticoagulation, wound necrosis anticoagulant subcutaneous tissue, abdomen, buttocks, legs, debridement therapy within the venules and deep thighs, mammary tissue preceding 24–48 veins, endothelial cell hours damage, red blood cell extravasation Wounds UK | Vol 14 |No 3|2018 14 Wounds UK |Vol idiopathic calcinosis Figure with 1.Handofapatient (Walshe and Fairley, 1995). 1995). andFairley,