Uncommon causes of ulceration
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7541.594 (Published 09 March 2006) Cite this as: BMJ 2006;332:594All rapid responses
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Dear Sir,
In this article about uncommon causes of ulceration, calciphylaxis (
calcific uraemic arteriolopathy,CUA) was cited as a cause. This does cause
painful ulcers on the lower limbs and abdominal skin of patients with
chronic kidney disease and diabetes. The histology of CUA shows
calcification in the medial layer of the small arterioles with intimal
hyperplasia, changes which can be seen in a wider area than the ulcerated
area. These changes predispose to thrombosis in these vessels and the
typical clinical picture. The deposition of the calcium in the walls is an
organised process so does not cause calcium deposits at the site of the
ulceration. Dystrophic calcification can occur at the site of ulceration
which is probably what is shown in the illustration. Treatment is
difficult with pain relief, local debridement and infection control being
important, but there is high mortality.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR –Patel et al pointed out cancers as unusual underlying causes
of skin ulcers in their recent article1. He gave non-melanoma skin
cancers and metastases as examples. I would also like to include malignant
melanoma (MM) in addition to the above, after personally witnessed several
cases of ulcerated lesions which turned out to be MM after diagnostic
biopsy during my dermatology attachment.
Although MM is less common than other skin cancers, it is the major
cause of skin cancer mortality and is potentially curable if diagnosed and
treated early2. Several authors reported detailed descriptions of MM that
presented as atypical ulcers. Kong et al. reported six cases of acral
melanoma presenting as chronic foot ulcers in both diabetic and non-
diabetic patients3. Zellman reported a case of amelanotic ulcer
presenting as an enlarging bleeding ulcer4. MM may be overlooked when
they develop in atypical locations or present with unusual appearances
such as vascular, non-pigmented, or ulcerated lesions which lack the
classical clinical features of a changing mole (Asymmetry, Border
irregularity, Colour variation, Diameter enlargement, and Elevated
surface)5.
The overall prognosis of atypical MM tends to be poorer than its
pigmented counterparts. This is due to delayed diagnosis, and ulcerations
being an indication of invasive disease with advanced TMN stage. Moreover,
advanced MM is often resistant to current treatment2.
This emphasise the importance of maintaining a high level of suspicion in
order to recognise malignant causes of skin ulcers. Further studies and
guidance may be helpful in determining the alarming features of ulcers
suggestive of malignancies, which would prompt referral to dermatologists
for diagnostic biopsy.
1. Patel GK, Grey JE, Harding KG. Uncommon causes of ulceration. BMJ
2006; 332:594-596
2. Roberts DLL, Anstrey AV, Barlow RJ, Cox NH. UK guidelines for the
management of cutaneous melanoma. Br J Dermatol 2002:146:7 – 17.
3. Kong MF, Jogia R, Jackson S, Quinn M, McNally P, Daview M.
Malignant melanoma presenting as a foot ulcer. Lancet 2005;366:1750.
4. Zellman GL, Houston MD. Amelanotic melanoma in a black man. J Am
Acad Dermatol 1997;37:665 - 6.
5. Grant-Kels JM, Bason E, Grin CM. The misdiagnosis of malignant
melanoma. Am Acad Dermatol 1998;40:539 - 48.
Competing interests:
None declared
Competing interests: No competing interests
Editor – In their article on uncommon causes of ulceration, Patel and
colleagues (1) include a table listing eight coagulation factors that are
associated with skin necrosis. Whilst skin necrosis can be seen in
association with coagulation factor deficiencies, this is very rare and is
usually only seen with severe reduction in the concentration of protein C
or protein S. This can occur due to inherited homozygous or acquired
deficiency of proteins C/S following warfarin initiation or infection,
most frequently due to meningococcal septicaemia (purpura fulminans). A
very small number of single case reports suggesting an association with
factor V Leiden/activated protein C resistance have been published (2,3),
but this association remains unproven considering that 3-5% of the
population of Europe and North America carry this mutation.
We do not believe true skin necrosis has ever been described in
antithrombin deficiency or in association with raised levels of
homocysteine or prothrombin. Although heparin cofactor II and factor XII
deficiency are also listed in the table, these two conditions are not
known to be associated with any clinical phenotype even when completely
absent from the circulation.
Alexander Gatt, Clinical research fellow,
Joost J van Veen, Clinical research fellow,
,br>Michael Makris, Reader
Sheffield Haemophilia and Thrombosis Centre,
Royal Hallamshire Hospital,
Glossop Road,
Sheffield, S10 2JF
References:
1. Patel GK, Grey JE, Harding KG. Uncommon causes of ulceration. BMJ 2006;
332:594-596
2. Makris M, Bardhan G, Preston FE. Warfarin induced skin necrosis
associated with activated protein C resistance. Thromb Haemost 1996;
75:523-524
3. Freeman BD, Schmieg RE, McGrath S, Buchman TG, Zehnbauer BA. Factor V
Leiden mutation in a patient with warfarin-associated skin necrosis.
Surgery 2000; 127:595-6
Competing interests:
None declared
Competing interests: No competing interests
Treatment of ulcers is 'bread and butter' for the plastic surgeon. I
found this article particularly interesting. It high-lighted to me the
importance of thinking laterally when dealing with a common every day
problem and remembering the more unusual causes. Next time I review a
patient with a chronic non-healing ulcer, I will consider carefully the
underlying cause.
Competing interests:
None declared
Competing interests: No competing interests
Re:Calciphylaxis and ulceration
The Purpose of this web site is to inform the public and those of
concern all about Calciphylaxis. How it appears, what it looks like and
how it is treated. The foundation is a Charity (501(c) set up to pass out
brochures and posters to dialysis centers across the United States. They
will also be sent to Hospitals for ICU units to post for easy recognition
and to Dermatology and other departments that may need to diagnose
Calciphylaxis. Our intention is to save as many lives as possible through
early diagnosis, so they can start treatment. In my husband's care they
waited 5 weeks to diagnose him and that was too late, he lost his life. I
named the foundation after him in hopes of saving as many lives as
possible in his name.
Competing interests: web site www.RonaldCHodesFoundation.com