Genetic Diseases

Recommendations

Identify and Treat the Cause
1 Take a careful history (venous/ arterial characteristics, other diagnoses, infection, medication, coexisting diseases, factors that may impair wound healing). Level of Evidence
Not Assessed
2 Consider genetic causes when leg ulcers are seen in children and young adults. Level of Evidence
Not Assessed
3 For nonhealable or maintenance wounds, provide support, pain control and modified local care (conservative debridement, bacterial and moisture reduction). Level of Evidence
Not Assessed


Address Patient-centered Concerns
4 Communicate (patients, family, caregivers) to establish a social support system with realistic expectations for healing and to prevent leg ulcer recurrences. Level of Evidence
Not Assessed
5 Assess / control pain and optimize activities of daily living Level of Evidence
Not Assessed


Provide Local Wound Care
6 Assess and document the wound at regular intervals. Level of Evidence
Not Assessed
7 Optimize local wound care: debridement, inflammation / infection control, and moisture balance. Consider biopsy of appropriate active (including biologicals) & adjunctive therapies if the wound is not healing at the expected rate. Level of Evidence
Not Assessed


Provide Organizational Support
8 Consult appropriate disciplines to maximize healing (e.g. mobility and nutrition). Level of Evidence
Not Assessed


Background

Many genetic conditions have been associated with skin ulceration and should be considered when leg ulcers, especially recurrent ulcers, are seen in children or young adults. Some of these disorders are described below.

♦ Hypercoagulability A variety of genetic clotting disorders may be associated with a history of recurrent DVT and an increased risk of venous leg ulcers, including Factor V Leiden; prothrombin G20210A mutation; antithrombin, protein C, or protein S deficiency; and hyperhomocysteinemia. Exercise programs, compression hose, smoking cessation, and avoidance of estrogen therapy can reduce the risk of DVT. Long-term anticoagulation may be necessary.

♦ Hematologic disorders Several inherited forms of anemia have been linked to the development of leg ulcers, including thalassemia and sickle cell anemia. In sickle-cell disease, deoxygenation of abnormal hemoglobin causes formation of sickle-shaped cells, which may not be flexible enough to traverse the microcirculation. The resulting vaso-occlusive crisis causes tissue injury and pain. Painful ulcers in anemic young individuals of African descent suggest sickle cell disease, and a blood smear demonstrating sickle-shaped red blood cells confirms the condition. Wound care for patients with this multisystem disease requires a team approach. Management of sickle-cell disease includes patient education, support and genetic counselling; management of pain and, possibly, depression and anxiety; and monitoring and management of organ involvement.

♦ Klinefelter syndrome Leg ulcers in Klinefelter syndrome result from a combination of factors, including chronic venous insufficiency, obesity, arterial dysplasia in the legs, and decreased fibrinolysis due to increased levels of plasminogen activator inhibitor-1 (PAI-1).

♦ Felty syndrome describes the triad of rheumatoid arthritis, splenomegaly and neutropenia. Leg ulcers in patients with this syndrome appear to have a multifactorial etiology, which includes venous insufficiency, vasculitis, arterial insufficiency and diabetes.

♦ TAP 1 mutation Mutations in a subunit of the transporter associated with antigen processing is associated with recurrent bacterial respiratory infections and granulomatous skin lesions that begin as a small pustule or subcutaneous nodule and progressively extend and ulcerate. These lesions are most often distributed asymmetrically over the legs.

♦ Leucocyte adhesion deficiency syndrome type 1: This deficiency is associated with recurrent bacterial and fungal infections and chronic leg ulcers.

♦ Werner’s syndrome, a rare genetic premature aging disorder, is associated with atrophic skin and subcutaneous tissue and the development of chronic foot ulcers.

References

Essential Publications
1 Klinefelter Syndrome Quality Indicator
 Type: Case-control study (2 groups)
Zollner TM, Veraart JC, Wolter M, Hesse S, Villemur B, Wenke A, Werner RJ, Boehncke WH, Jost SS, Scharrer I, Kaufmann R. Leg ulcers in Klinefelter’s syndrome – further evidence for an involvenment of plasminogen activator inhibitor-1. British journal of dermatology 1997; 136(3): 341-344.
This report found that Plasminogen Activator Inhibitor-1 (PAI-1) activity is not elevated in Klinfelter’s syndrome in general; elevation of PAI-1 activity in patients suffering from Klinefelter’s syndrome does not appear to be secondary to PAI-1 influencing parameters; elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter’s syndrome. Overall, a therapy for leg ulceration in Klinefelter’s syndrome that aims to return the elevated PAI-1 activity to normal should be explored.
2 Felty Syndrome Quality Indicator
 Type: Case-control study (2 groups)
Chin-Yee I, Halasi S and Hassan A. Successful Treatment of Perianal Ulcers in a Patient with Felty’s Syndrome Using Granulocyte Colony Stimulating Factor. J Clin Rheumatol 1996; 2: 283-288.
Intermittent use of Granulocyte Colony Stimulating Factor (G-CSF) may be a useful therapy for patients who have Felty’s Syndrome and develop complications from their neutropenia. G-CSF contributed to an increase in neutrophil counts and gradual healing of ulcers. Discontinuation of the G-CSF resulted in a return to the baseline neutropenic site without recurrence of ulceration.


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