metabolic + systemic disease - calcium, mucin, porphyrias,

Question 1

How do you structure disorders of calcification?

Answer 1

Those with normal calcium homeostasis
– secondary to inflammation (DM, CREST, scleroderma, LE, PCT, morphea, LS, pancrealitis, RA, fat necrosis)
– secondary to infection (onchocerciaasis)
– tumours (hair follicle cysts - pilomatricoma, BCC, epidermoid cyst, pyogenic granuloma, Seb K, AFX, ,elanoma, pilar cysts)
– genetic - PXE, ehlers danlos, Werner, Down Syndrome (miliary calcinosis)
– trauma/injection (eg peel prick, burns, keloids)
–idiopathic - scrotal calcinosis, miliary calcinosis
Those with abnormal calcium homeostasis
– metastatic calcification
– calcinosis cutis
– calciphylaxis

Question 2

What Ix would you perform in calcinosis cutis?

Answer 2

• check for underlying cause
• Serum calcium, urinary calcium, Vit D, PTH, phosphate, XR, U+E, ALP
• xray to define
• Skin bx - Von Kossa stain

Question 3

Mx of idiopathic cutaneous calcinosis / hypercalcemia

Answer 3

• local wound care
• surgical excision
• CO2 laser, lithotripsy
• topical 10% sodium thiosulphate
• IL sodium thiosulphate (0.1ml 25% solution)
• IV sodium thiosulphate 3x/week
• Ca channel blockers
• bisphosphonates (reduce OC activity + increase OB activity)
• low calcium diet
• cinacalcet (reduces PTH)
• sevelamer (binds phosphate)
• parathyroidectomy

Question 4

How does sodium thiosulphate work?

Answer 4

Formation of highly soluble calcium thiosulfate (calcium chelating agent) + vasodilation + antioxidant

Question 5

What are the causes of hypercalcemia? (ie disorders of calcium homeostasis)

Answer 5

Hyperparathyroidism
Hypervitamin D
Sarcoid
Bone metastases
Hyperphosphatemia

Question 6

How do disorders of calcium metabolism present - what are the clinical presentations of hypercalcemia

Answer 6

Bones, stones, groans + psychic moans

Calcinosis cutis

Question 7

What is the pathophysiology of calciphylaxis?

Answer 7

Systemic clacium abnormalities are common but not always present

Uraemic variant - associated with renal failure + haemodialysis
Non-uraemic variant

Triggers/associations

• Hyperparathyroidism
• High Vitamin D
• Drugs - warfarin, Vit D supps, IVIg, steroids
• Diabetes
• Obesity
• Malignancy
• Liver failure

Question 8

What is the histology for calciphylaxis?

Answer 8

Much more subtle than dystrophic calcification/ calcinosis cutis
Calcium intravascularly + in the walls of vessels - calcium appears blue on H+E
Cutaneous necrosis
Staining = von kossa

Question 9

What are the clinical features of calciphylaxis?

Answer 9

livedo due to vascular thrombosis
retiform purpura (uninflamed)
ulceration - irregular, stellate, deep
necrosis
extreme pain 
common sites = abdomen, thighs (also penis, breasts, tongue, internal organs)

Question 10

What are the complications of calciphylaxis?

Answer 10

Mortality is HIGH (80%)
Due to infective complications + sepsis
Pain
Internal organ involvement

Question 11

What are the DDx for calciphylaxis

Answer 11

Retiform pupura + skin necrosis

Warfarin/ heparin necrosis, other vasculopathy/ vasculitis , hypertensive ulcer of martorell, PG, necrotising fasciitis,

PG - common on legs, any age, severe pain, purpuric/raised/undermined edges, inflamed, presence of association
Warfarin necrosis - breast/hip/buttocks/thighs, moderate pain, erythematous edge though no other surrounding skin changes, histo - fibrin, thrombi
Martorell ulcer - severe pain, lower legs, older patient, border is purpuic/livedo surroudning, HTN in pt, histo shows arteriosclerosis + intimal thickening/ luminal narrowing

Question 12

Ix of calciphylaxis?

Answer 12

Confirm diagnosis/exclude differentials

• incisional biopsy
• Xray (reticular/net-like calcification)
• swab for m/c/s

Check for triggers + associations

• HbA1c, OGTT, BSL
• serum calcium, ELFTs, FBC, PTH, vitamin D, ALP, phosphate, urinary calcium
• coags
• age-appropriate malignancy screen
• serum EPP/ immunofixation, blood film

Check for complications
- blood cultures, tissue cultures, swabs

Monitoring
- FBC, ESR, CRP

Question 13

Mx of calciphylaxis

Answer 13

Admit to hospital, medical ward
Referrals - pain, wound care nurses, renal, surgeons (if debridement needed), physio
Analgesia - will need pain team, often v painful
Wound care - antibacterial, soft debridement
Photographs to monitor
Optimise dialysis (calcium/phosphate)
Low calcium diet
Cease any precipitating drugs
IV sodium thiosulphate
Phosphate binders
Cinacalcet
Bisphosphonates
Parathyroidectomy
Anticoag (once excluded warfarin necrosis)
Pentoxyfilline
Treat secondary infection
Debridement of necrotic tissue

Question 14

How do you structure cutaneous mucinoses?

Answer 14

Primary + Secondary

• primary (Lergy SAL (DAIN), Rolls Snotty Toilet Paper, Silly Charlie Dog, Pick it Up
• – Lichen myxoedematosis - Scleromyxoedema, atypical myxoedema, localised lichen myxoedema (Discrete papular, Acral persistent, infancy variant, nodular)
• – REM (reticular erythematous mucinosis)
• – Scleroedema (of Buschke)
• – Thyroid associated mucinoses
• – Papular mucinosis of connective tissue diseases
• – Self healing juvenile cutaneous mucinosis
• – Cutaneous focal mucinosis
• – Digital myxoid cyst
• – Follicular mucinosis of Pinkus
• – Urticarial variant of follicular mucinosis

Question 15

Triggers/pathophys for scleromyxoedema vs lichen myxoedematosis

Answer 15

scleromyxoedema

• unknown pathophys
• strong association w monoclonal gammopathy - IgG lambda (also Waldenstrom, lymphoma, myeloma)
• – silicone breast implants, hyaluronic acid injections

Lichen myxoedematosis

• HIV, Hep C
• toxic oil exposure