Correspondence

Heparin-Induced Skin Necrosis

N Engl J Med 1997; 336:588-589February 20, 1997

Article

To the Editor:

In the September 5 Image in Clinical Medicine1 the appearance of the skin lesion described as heparin-induced skin necrosis is also compatible with a diagnosis of ecthyma gangrenosum. The authors do not state whether the heparin injected was sterile or whether cultures of aspirates from the skin lesion grew gram-negative organisms. This information would be useful for the differential diagnosis.

Richard V. McCloskey, M.D.
Centocor, Malvern, PA 19355-1307

1 References

1. 1

   Christiaens GCML, Nieuwenhuis HK. Heparin-induced skin necrosis. N Engl J Med 1996;335:715-715
   Full Text | Web of Science | Medline

To the Editor:

With respect to the image of heparin-induced skin necrosis, the authors should have considered other causes, since the initial injections of heparin apparently did not result in similar lesions. The morphology and clinical course of a cutaneous lesion resulting in ulceration requiring skin grafting resemble those of ecthyma gangrenosum observed in cases of Pseudomonas aeruginosa septicemia. Was the patient immunosuppressed? Did she have any associated systemic symptoms or neutropenia? Did she receive any antibiotic therapy before or after the appearance of the skin lesion?

Similar lesions are also possible in primary cutaneous infections with P. aeruginosa (primary P. aeruginosa pyoderma), other gram-negative rods such as Escherichia coli, klebsiella, or even fungi. Did the authors perform Gram's staining and culture of the aspirate from the lesion? Secondary infection from a contaminated needle or some other source is always a possibility in hospitals. Biopsy of the lesion might have documented large numbers of bacteria invading the blood vessels, with few inflammatory cells in the case of ecthyma gangrenosum.1

Furthermore, the estimations of protein C and protein S mentioned in the report seem irrelevant, since deficiencies of these proteins predispose patients to skin necrosis after warfarin therapy and not heparin. Warfarin given alone in those situations causes a further decrease in protein C or protein S concentrations (since they are dependent on vitamin K), leading to thrombosis of veins and capillaries supplying blood to the skin and resulting in extensive necrosis.

P. Dileep Kumar, M.D.
Sur Central Hospital, Sur, PB 259 Code 411, Oman

1 References

1. 1

   Pollack M. Pseudomonas infections. In: Isselbacher KJ, Martin JB, Braunwald E, Fauci AS, Wilson JD, Kasper DL, eds. Harrison's principles of internal medicine. 13th ed. Vol. 1. New York: McGraw-Hill, 1994:665-71.
   

To the Editor:

Do the authors know for a fact that heparin was given? Could the patient have received a subcutaneous injection of a vasoactive, vasoconstrictive agent, such as epinephrine?

Frederick G. Schechter, M.D.
University of California, Irvine, Irvine, CA 92717

To the Editor:

The image of heparin-induced skin necrosis is a striking and instructive example of this clinical problem. However, the report would have been made more complete by the inclusion of skin-biopsy findings on this bullous lesion for both routine hematoxylin-and-eosin staining and immunofluorescence microscopy to establish the diagnosis.

Despite the clear-cut history of recent heparin injections at the lesion site, the lesion might have had other causes — bullous erythema multiforme, pemphigus vulgaris, and bullous impetigo to name just a few. Since a skin graft was necessary to repair the lesion, a definitive diagnosis is imperative. Histologic findings in heparin-induced necrosis include extensive thrombosis of the dermal and subcutaneous vessels, with hemorrhage and focal epidermal necrosis but no evidence of vasculitis or an inflammatory infiltrate.1

Robert Lee Carter, M.D.
1515 Chain Bridge Rd., McLean, VA 22101

1 References

1. 1

   Gold JA, Watters AK, O'Brien E. Coumadin versus heparin necrosis. J Am Acad Dermatol 1987;16:148-150
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Drs. McCloskey and Kumar that infectious causes should be considered in the differential diagnosis of erythematous, necrotic skin lesions after an injection. In this case there were no indications of an infection, the patient was otherwise healthy and was not immunocompromised, and cultures were negative for pathogens.

With respect to the comment of Dr. Schechter, we believe it is very unlikely that the patient was given an injection of epinephrine instead of heparin. A skin biopsy may be helpful if one is doubtful about the diagnosis of a heparin-induced skin lesion, but it is usually not necessary. Heparin-induced skin lesions at injection sites typically begin five or more days after the initiation of treatment. The lesions may appear as painful erythematous plaques or skin necrosis. Heparin-dependent platelet-activating antibodies may be present. This adverse effect is not uncommon; Warkentin1 observed it in six patients over a 30-month period.

H. Karel Nieuwenhuis, M.D., Ph.D.
G.C.M. Lieve Christiaens, M.D., Ph.D.
University Hospital Utrecht, 3508 GA Utrecht, the Netherlands

1 References

1. 1

   Warkentin TE. Heparin-induced skin lesions. Br J Haematol 1996;92:494-497
   CrossRef | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Ashley Wysong, Priya Venkatesan. (2011) An approach to the patient with retiform purpura. Dermatologic Therapy 24:2, 151-172
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2. 2

   2006. Heparins. , 1590-1600.
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3. 3

   Zahida Khan, D. K. Watson. (2000) Heparin-induced skin necrosis. BJOG: An International Journal of Obstetrics and Gynaecology 107:10, 1315-1316
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4. 4

   Jeanine M. Walenga, Rodger L. Bick. (1998) HEPARIN-INDUCED THROMBOCYTOPENIA, PARADOXICAL THROMBOEMBOLISM, AND OTHER SIDE EFFECTS OF HEPARIN THERAPY. Medical Clinics of North America 82:3, 635-658
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