Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
doi: 10.4103/0378-6323.27755
PMID: 17050933

Leg ulcers due to hyperhomocysteinemia

DS Krupa Shankar, Syed Akhib
 Department of Dermatology, Manipal Hospital, Bangalore, Karnataka, India

Correspondence Address:
D S Krupa Shankar
Department of Dermatology, Manipal Hospital, 98 Rustom Bagh, Airport Road, Bangalore-560 017, Karnataka
How to cite this article:
Krupa Shankar D S, Akhib S. Leg ulcers due to hyperhomocysteinemia. Indian J Dermatol Venereol Leprol 2006;72:367-369
Copyright: (C)2006 Indian Journal of Dermatology, Venereology, and Leprology


Chronic leg ulcers are rare in young adults and generally indicate a vascular cause. We report a case of a 26-year-old man with leg ulcers of eight months duration. Doppler study indicated venous incompetence and a postphlebitic limb. However, as the distribution and number of ulcers was not consistent with stasis alone and no features of collagen vascular disease were noted, a hyperviscosity state was considered and confirmed with significantly elevated homocysteine level in the serum. Administration of vitamins B1, B2, B6 and B12, trimethyl-glycine, mecobalamine, folic acid and povidone iodine dressings with culture-directed antibiotic therapy led to a satisfactory healing of ulcers over a period of one month. Hyperhomocysteinemia must be considered in the differential diagnosis of leg ulcers in young individuals.
Keywords: Hyperhomocysteinemia, Hyperviscosity syndrome
Healing ulcers after 4 weeks of treatment
Healing ulcers after 4 weeks of treatment
Cutaneous ulcers on the medial aspect of left knee
Cutaneous ulcers on the medial aspect of left knee


Hyperhomocysteinemia is a disorder of methionine metabolism and its metabolites (homocysteine, homocysteine-cysteine complex and others). The accumulation of homocysteine and its metabolites is caused by disruption of any of the three interrelated pathways of methionine metabolism. Deficiency in the cystathionine B-synthase (CBS) enzyme, defective methylcobalamin synthesis or abnormality in methylene tetrahydrofolate reductase leads to accumulation of homocysteine in blood.

Case report

A 26-year-old businessman presented with multiple episodes of ulcerations over the left leg during the last 14 months. After the first episode 14 months back he was in remission for six months. The ulcers began on the dorsum of the left foot, medial malleoli-medial aspect of the knee and showed purulent discharge at all times. He was treated by a dermatologist with topical betamethasone and topical beclomethasone dipropionate, clotrimazole, neomycin and oral antibiotics. He had a Doppler study carried out at the age of 19 years and was diagnosed to have deep vein thrombosis and treated with acenocoumarol for one year.

On examination, the patient was obese. He presented with multiple varicosities, discoloration and cutaneous ulcers with surrounding induration on the left lower limb. There were 13 ulcers of which the biggest ulcer measured 3 x 8 cm in diameter with pale granulation, yellowish slough, greyish edge, a halo of erythema and induration [Figure - 1]. Similar lesions were seen on the medial malleoli, shin and multiple ulcers on the lateral aspect of the left foot [Figure - 2]. His systemic examination was unremarkable. There was no family history of diabetes mellitus, hypertension, atopy or stroke. He was a nonsmoker and nonalcoholic.

Keeping in mind the known causes of leg ulcers we went on to investigate him with a duplex color Doppler, which demonstrated venous incompetence and postphlebitic sequelae in the lower limb. Stasis per se seemed inadequate to account for the number and distribution of ulcers, hence a hyperviscosity syndrome was considered and the following investigations were done. Investigations showed anti-cardiolipin IgA: 3.866 apl (10), anti-cardiolipin IgM: 1.269 mpl (7), anti-cardiolipin IgG: 1.018 gpl (10), anti-thrombin III function 92% (80-100%), lupus anti-coagulant: 29 seconds (29), protein S activity 123.6% (65-140%) and T3 T4 TSH was within normal range. Protein C activity 68.2% (70-130%) was marginally but not significantly low. Electrocardiogram (ECG) was normal. Random blood sugar was 179 mg/dl (70-150), random urine sugar (0.5%) suggestive of stress diabetes or insulin resistance. Lipid profile showed total cholesterol 222 mg/dl (< 200), triglycerides 251 mg/dl (< 200), HDL cholesterol (Direct) 29 mg/dl (35-55), LDL cholesterol 143 mg/dl (< 130), VLDL Cholesterol 50 mg/dl (10-40), Total cholesterol: HDL cholesterol ratio 7.65:1 (< 6.0).

Culture from the ulcer grew Staphylococcus aureus and Pseudomonas aeruginosa that were sensitive to a few antibiotics, of which ciprofloxacin 1g once daily for 10 days was chosen for treatment. The plasma homocysteine level was> 50 (normal range 0-17) and hence a diagnosis of homocysteinemia was made. He received trimethyl glycine 500 mg, mecobalamine 500 mcg, folic acid 1 mg, pyridoxine hydrochloride 10 mg, ciprofloxacin and injections of vitamin B3, B12, vitamin C, niacinamide, acenocoumarol and dextropropoxyphen to relieve his pain. Povidone iodine dressings and collagen Type III dressings were done twice a week.

The ulcer on the medial aspect of the knee healed after four weeks with some atrophy and hyperpigmentation [Figure - 1]a. At the time of ulceration some areas with erythema and overlying suppuration, erosions healed up without breaking down to ulcer. The ulcer in the region of medial malleoli had healed significantly at the end of six weeks. The multiple ulcers on the lateral aspect of the left foot had healed satisfactorily [Figure - 2]a. The patient remains well one and a half years later.


Homocysteine is a sulfur-containing metabolite of methionine and hyperhomocysteinemia is a risk factor for atherosclerosis and venous thrombosis.[1] It can be caused by genetic disorders affecting the trans-sulfuration or remethylation pathways of homocysteine metabolism, folic acid deficiency, vitamin B12 deficiency, renal failure, hypothyroidism, increasing age and smoking.[2]

Hyperhomocysteinemia is a biochemical disorder resulting from deficiency of cystathionine-beta-synthase. The metabolic effects include increased platelet aggregation, toxic damage to endothelial surfaces[3] and altered anti-thrombin III activity leading to thromboembolic phenomenon. The systemic effects are as follows:

a) CVS: Myocardial infarction;[4] hypertension; stroke;[4] blindness, renal, portal or pulmonary embolism, deep vein thrombosis.

b) Ocular: Ectopia lentis, myopia, retinal detachment

c) Skeletal: Marfanoid habitus, osteopenia

d) Skin: Malar flush, livedoid vasculitis,[5] canities

e) CNS: Mental retardation, seizures and stroke.[6]

Hyperhomocysteinemia is generally recognized as an independent risk factor for coronary, cerebral and peripheral atherosclerosis. There has recently been renewed interest in homocysteine metabolism because hyperhomocysteinemia has been associated with occlusive arterial disease and neural tube defects. Deficiency of the enzyme 5, 10-methylenetetrahydrofolate reductase results in hyperhomocysteinemia and a wide variety of neurological and vascular symptoms. Molecular genetic analysis of the enzyme has led to the identification of nine rare mutations associated with a severe deficiency phenotype as well as one common mutation (found in 35 to 40% of alleles in the general population) that is proposed as a risk factor in some forms of cardiovascular disease and in neural defects.[3]

Folic acid acts by participating in the synthesis of DNA, RNA and proteins. It is necessary for DNA repair, replication maintaining integrity of genome.[7] Complications of hyperhomocysteinemia are inflammatory bowel disease, cerebral thrombosis, acute myocardial infarction, venous thrombosis and atherosclerosis. The associated disorders of hyperhomocysteinemia are thromboembolism, pulmonary embolism, schizophrenia, Parkinson′s disease, stroke, diabetes mellitus, osteoporosis, scoliosis, kyphosis, spina bifida, lens dislocation, glaucoma and myopia. Strategies for the treatment of CBS deficiency include increasing residual enzyme activity by giving pyridoxine in those patients with vitamin responsive variants, reducing the load on the affected pathway with a low methionine diet and supplementing the diet with cysteine and giving betaine in order to utilize alternative pathways to remove homocysteine.[8]

All patients with chronic multiple leg ulcers with features suggestive of other vascular phenomena such as deep vein thrombosis, venous ulcer, stasis dermatitis, ischemic heart disease, retinal artery occlusion, claudication and Raynaud′s phenomenon should have plasma homocysteine level measured immaterial of the age of the patient. It should also be considered in patients in whom basic investigations for the common causes of leg ulcers are not conclusive. Given the low cost of investigation and the easy prevention with folic acid, plasma homocysteine must be measured in every patient with chronic leg ulcers as it may be a contributory and correctable if not a primary cause of chronic leg ulcers.

Ray JG. Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med 1998;158:2101-6.
[Google Scholar]
Rozen R. Molecular genetic aspects of hyperhomocysteinemia and its relation to folic acid. Clin Invest Med 1996;19:171-8.
[Google Scholar]
de Groot PG, Wilems C, Boers GH, Gonsalves MD, van Aken WG, van Mourik JA. Endothelial cell dysfunction in homocystinuria. Eur J Clin Invest 1983;13:405-10.
[Google Scholar]
Melo M, Gaspar E, Madeira S, de Moura P, Alexandrino B, de Moura JJ. The methylenetetrahydrofolate reductase (MTHFR) 677C T mutation and cardiovascular risk-A case of ischemic stroke and acute myocardial infarction. Rev Port Cardiol 2005;24:89-99.
[Google Scholar]
Gibson GE, Li H, Pittelkow MR. Homocystinemia and livedoid vasculitis. J Am Acad Dermatol 1999;40:279-81.
[Google Scholar]
Abbott MH, Folstein SE, Abbey H, Pyeritz RE. Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: Prevalence, natural history and relationship to neurologic impairment and vitamin B6- responsiveness. Am J Med Genet 1987;6:959-69.
[Google Scholar]
Wang G, Dai J, Mao J, Zeng X, Yang X, Wang X. Folic acid reverses hyper - responsiveness of LPS-induced secretion from monocytes in patients with hyperhomocysteinemia. Atherosclerosis 2005;179:395-402.
[Google Scholar]
Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, et al . Hyperhomocysteinemia: An independent risk factor for vascular disease. N Engl J Med 1991;324:1149-55.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections