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Clinical Vignette
A 40-year-old woman is referred for evaluation and management of diabetes mellitus. She has had diabetes for 8 years—it was diagnosed during her last pregnancy. Her medications include metformin, 1000 mg twice daily, and glyburide, 5 mg twice daily. She has not being doing regular home blood glucose monitoring; however, when she does check, the glucose value is typically greater than 200 mg/dL (>11.1 mmol/L). A recent hemoglobin A1c measurement was 9% (75 mmol/mol).
The patient’s main concern is skin lesions on her lower legs that began 8 years ago, during her last pregnancy. She has plaquelike lesions on both shins. The plaques have been slowly enlarging. There is no associated pruritus or pain, and the lesions themselves are asymptomatic but she is embarrassed to have bare legs in public.
On physical examination, her height is 65 in (165.1 cm) and weight is 233 lb (105.9 kg) (BMI = 40 kg/m2). Her blood pressure is 130/84 mm Hg, and pulse rate is 78 beats/min. Mild background retinopathy is present on eye examination. She has no axillary or inguinal lymphadenopathy. Skin lesions are limited to the anterior lower legs. There are multiple discrete and confluent red to brown atrophic annular plaques (see image). The borders are brown and not erythematous. The centers of the plaques are atrophic. There is no ankle edema.
On the basis of clinical presentation and physical examination findings, it is appropriate to advise the patient that:
Her skin lesions will improve if she improves her glycemic control
These are café-au-lait spots and she is at risk for neurofibromatosis type 1
Treatment includes topical or intralesional administration of corticosteroids
Her skin condition is more common in men
The skin findings are consistent with stasis dermatitis
This patient has typical necrobiosis lipoidica (NL), a chronic granulomatous disorder of the skin. Frequently associated with diabetes mellitus, NL was previously referred to as necrobiosis lipoidica diabeticorum (NLD); however, NL can occur in the absence of diabetes and “diabeticorum” has been dropped from the name.
: Dr. Edward Harper Rynearson (circa 1950). [Image provided courtesy of the W. Bruce Fye Center for the History of Medicine and the Libraries History of Medicine Collection at Mayo Clinic, Rochester, Minn.]Edward H. Rynearson (Endocrine Society President 1950-1951) coauthored a landmark 27-page report on NLD in 1940. First described by Oppenheim in 1929, NLD was initially termed dermatitis atrophicans lipoides diabetic. In 1932, Urbach coined the term NLD, which persisted until the recent transition to NL. Rynearson’s publication in 1940 summarized the 8 patients with NLD who had been diagnosed at Mayo Clinic and 78 patients who had been reported in the literature. The occasional lack of diabetes was highlighted by Rynearson in 13% of those 86 cases. As noted by Rynearson, NL is more common in women than in men (3:1) (thus, Answer D is incorrect). In persons with diabetes, the average age of onset of NL is 25 years; in persons without diabetes, it is 45 years. In 1940, Rynearson concluded that, “the pathogenesis of this condition remains obscure.” Although many theories on pathogenesis have come and gone, Rynearson’s conclusion remains true to this day.
A subject of multiple New England Journal of Medicine “Images in Clinical Medicine” over the years, the clinical picture of NL is classic and unmistakable. These lesions should never be confused with café-au-lait spots (Answer B); they are typically asymptomatic and appear as well-circumscribed yellow-brown telangectatic plaques with central atrophy and raised violaceous borders. NL is most frequently located on the shins and dorsum of the feet. Other locations include the trunk, upper extremities, scalp, face, and genitals. With trauma, the lesions may ulcerate. Older lesions become flat and depressed and appear yellow-orange in color. The differential diagnosis includes other granulomatous disorders that involve the skin (e.g., granuloma annulare, cutaneous sarcoidosis, necrobiotic xanthogranuloma), pigmented purpuric dermatosis, and stasis dermatitis. Cutaneous sarcoidosis is very rare and when it occurs, it is usually in the setting of multisystem involvement (eg, lymphadenopathy, lung, eyes)—findings absent in this patient. Necrobiotic xanthogranuloma is typically associated with an IgG monoclonal gammopathy and the skin lesions usually are periorbital. Pigmented purpuric dermatosis is usually distinguished from NL by its purpura, petechiae, and brown discoloration. Stasis dermatitis (Answer E) is associated with chronic venous insufficiency and is typically dark brown in color and associated with edema—findings absent in this patient.
In 1940, Rynearson and colleagues noted that, “The lesions tend to run a chronic course and neither local therapy nor, in the case of diabetics, general management tended to speed their healing. In some cases the lesions slowly receded and left depressed scars.” Unfortunately, 75 years later, the observations are essentially the same. There is no cure for NL. The goals of treatment for nonulcerated NL are to improve the appearance, control active inflammation, and decrease the risk for ulceration. Inflammation can be partially controlled with the administration of either topical or intralesional corticosteroids (Answer C). Although the patient in this vignette needs to improve her glycemic control, it will not affect her NL (thus Answer A is incorrect).
Educational Objective: Diagnose necrobiosis lipoidica on the basis of the clinical presentation and appearance on physical examination.
Historical Context Dr. Edward H. Rynearson, Endocrine Society President 1950-1951
Edward Harper Rynearson, MD (Endocrine Society President 1950-1951)—known by most as “Eddie”—was born in Pittsburgh, Pennsylvania, on April 27, 1901. He earned his bachelor of arts degree from Ohio Wesleyan University in 1922 and his MD degree from the University of Pittsburgh in 1926. He interned at Mercy Hospital in Pittsburgh and came to Mayo Clinic in Rochester, Minnesota, on October 1, 1927, as a fellow in medicine in the Mayo Graduate School of Medicine. In 1930, Rynearson made first assistant in medicine, and in 1932 he was appointed to the Mayo Clinic staff. In 1947, he was appointed head of a section of medicine devoted to endocrinology and metabolism. From 1954 to 1962, Rynearson chaired all 3 endocrine sections.
Rynearson was a scholarly clinician. His areas of clinical interest included obesity, insulinoma, hypopituitarism, pituitary tumors, adrenal disorders, hyperparathyroidism, thyroid dysfunction, diabetes mellitus, dermatologic disorders in patients with diabetes, gynecomastia, Cushing syndrome, and the futility of prolongation of life when a fatal outcome was inevitable and imminent. He authored 46 peer-reviewed publications—literally covering the breadth of endocrinology. He took great pride in being a clinician and sharing the lessons he learned by caring for patients. Rynearson was concerned about the prevalence of health fads and the vitamin concoctions that were sold at exorbitant prices for “nutritional health” or as weight-loss aids. His last peer-reviewed publication came in 1974 and was titled: “Americans love hogwash.” In an interview with the Rochester Post-Bulletin, Rynearson was quoted as saying, “People want to be duped. They want super-health and there is no such thing.”
In 1950, he was elected president of the Endocrine Society. That was a time when the Endocrine Society was alternating the presidency between a clinician and a basic scientist in an effort to recognize clinical practice and basic science. However, soon after his presidency, this distinction was ignored and Rynearson was the last clinician of his era to become president of the Endocrine Society. He had a keen interest in and talent for public speaking. He was widely recognized as a colorful speaker with spontaneous wit and ready satire.
Rynearson and his flowers (circa 1972). [Image provided courtesy of the W. Bruce Fye Center for the History of Medicine and the Libraries History of Medicine Collection at Mayo Clinic, Rochester, Minn.]
Alexander Albert, MD, PhD, (Endocrine Society President 1970-1971) wrote in a memoriam, “As I review the last 40 years, the picture of Eddie that emerges is that of a wonderfully warm person, a kindly person, and a person generous to a fault. I never heard him say anything mean about anyone. Yet, he was a very sensitive man. If some arrows flew his way from nearby sources, he was hurt rather than angry. I have often thought that his sensitivity was due to an unwarranted modesty so that he underestimated his value. Clearly, this was contrary to the high value and esteem that his colleagues had for him.”
Rynearson retired from Mayo Clinic in July 1966. He was well known in Rochester for his passion for gardening and growing flowers—something that he continued to pursue in retirement. Rynearson was the first president of the Rochester Garden and Flower Club, and his dahlias won a championship award at the 1962 Minnesota State Fair.
Rynearson married Miss Lida Brickwell Repp on June 26, 1928. He and Lida had 4 children: Jean Harper (Mrs. Franklin Michaels of Rochester, Minnesota), Dr. Robert Repp Rynearson (of the Scott-White Clinic, Temple, Texas), Lida Ann (Mrs. Ben M. Cummins of Albuquerque, New Mexico), and Dr. Edward King Rynearson (Seattle, Washington). Rynearson died at age 86 as a result of injuries suffered in a motor vehicle accident in Ft. Meyers, Florida, on February 17, 1987.
References: Albert A. In memoriam: Edward H. Rynearson, M.D. J Clin Endocrinol Metab. 1988;66(3):653-654.
Gastineau CF, Rynearson EH. Obesity. Ann Intern Med. 1947;27(6):883-897.
Perkins RF, Rynearson EH. Practical aspects of insufficiency of the anterior pituitary gland in the adult. J Clin Endocrinol Metab. 1952;12(5):574-603.
Purnell DC, Randall RV, Rynearson EH. Postpartum pituitary insufficiency: (Sheehans’s syndrome): review of 18 cases. Mayo Clin Proc. 1964;39:321-331.
Rynearson EH. Hyperinsulinism among malingerers. Med Clin North Am. 1947;31:477-480.
Rynearson EH. You are standing at the bedside of a patient dying of untreatable cancer. CA Cancer J Clin. 1959;9(3):85-87.
Rynearson EH. Americans love hogwash. Nutr Rev. 1974;32(0)(Suppl 1):1-14.
Troen P, Rynearson EH. An evaluation of the prophylactic use of cortisone for pituitary operations. J Clin Endocrinol Metab. 1956;16(6):747-754.
Dissemond J. Images in clinical medicine. Necrobiosis lipoidica diabeticorum. N Engl J Med. 2012;366(26):2502.
Wake N, Fang JC. Images in clinical medicine. Necrobiosis lipoidica diabeticorum. N Engl J Med. 2006;355(18):e20.
Oppenheim. Eigentumliche disseminierte degeneration des bindegewebes der haut bei einem diabetiker, Zentralbl. F. Haut- u. Geschlechtskr. 32;179:1929-1930.
Urbach E. Bietrage zu einer physiologischen und pathologischen Chemie der Haut: X. Eine neue diabetische Stoffwechseldermatose: nekrobiosis lipoidica diabeticorum. Arch F Dermat U Syph. 1932;166:273-285.
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![: Dr. Edward Harper Rynearson (circa 1950). [Image provided courtesy of the W. Bruce Fye Center for the History of Medicine and the Libraries History of Medicine Collection at Mayo Clinic, Rochester, Minn.]](https://endocrinenews.endocrine.org/wp-content/uploads/rynearson-1-250x300.jpg)
![Rynearson and his flowers (circa 1972). [Image provided courtesy of the W. Bruce Fye Center for the History of Medicine and the Libraries History of Medicine Collection at Mayo Clinic, Rochester, Minn.]](https://endocrinenews.endocrine.org/wp-content/uploads/rynerson-2-195x300.jpg)
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