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From the Division of Endocrinology, Metabolism, Nutrition, and Internal Medicine (V.F.), Department of Dermatology (D.D.F.A.), and Section of Biostatistics (G.R.P.), Mayo Clinic, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: Dr. V. Fatourechi, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
Abstract
Little is known about the long-term outcome of patients with thyroid dermopathy, an extrathyroidal manifestation of Graves’ disease. Also, it is not known to what degree treatment promotes remission of the lesions. The present report supplies information on the natural course of mild, untreated and severe, treated thyroid dermopathy. In this study, we report on the outcomes of 178 patients seen at our institution between January 1969 and November 1995 with thyroid dermopathy who were followed up for an average of 7.9 yr. Nonpitting edema was the most prevalent form of dermopathy (43.3%), and the pretibial area was the region most commonly involved (99.4%). The majority of patients with dermopathy had ophthalmopathy (97.0%). Topical corticosteroids were the most commonly used treatment (53.9%). Patients with milder forms of dermopathy (40.4%) did not receive any therapy for dermopathy. Twenty-six percent of the patients experienced complete remission, 24.2% had moderate improvement (partial remission), and 50.0% had no or minimal improvement of their dermopathy at last follow-up. Patients who did not receive therapy experienced a significantly (P = 0.03) higher rate of complete remission (34.7%) than those who received local therapy (18.7%), although the combined complete and partial remission rates were not significantly different for the treated and untreated groups (P = 0.3). However, the treated and untreated groups were not comparable because our practice is to use therapy for more extensive and severe cases. All five cases of elephantiasis were in the treatment group and were less likely to have remission because of the severity of their skin condition. Patients receiving treatment were more likely to have dermatologic consultation and histologic diagnosis (P < 0.001). The beneficial effect of topical corticosteroid therapy on long-term remission rates remains to be determined.
LOCALIZED MYXEDEMA, OR thyroid dermopathy, is an infrequent manifestation of autoimmune thyroiditis and, in particular, of Graves’ disease. It is characterized by localized thickening of the skin (1, 2). Commonly localized in the pretibial area, it is therefore often referred to as pretibial myxedema (PTM). Various treatment modalities have been employed, including topical and systemic corticosteroids, compression dressings, and local injections (3, 4, 5, 6, 7). Moderate benefits of short-term topical corticosteroid therapy have been reported (3). We earlier reported a 10% complete remission rate after an average follow-up of 3.5 yr in a study of 150 patients seen between 1969 and 1989 (1). Information is needed about the natural course and long-term outcome of patients with this condition. Here we report on a 26-yr experience (1969–1995) with thyroid dermopathy. We specifically present data on long-term outcome of mild, untreated and severe, treated groups in this disorder after analysis of the information obtained from the last clinical evaluation and the response of the patients to questionnaires mailed in September 2000.
Patients and Methods
We retrospectively reviewed the records of all patients who had a discharge diagnosis of thyroid dermopathy or PTM between January 29, 1969, and November 15, 1995, at the Mayo Clinic. Patients seen before 1989, who were subjects of a previous report (1), are included in the present study. Additionally, we mailed questionnaires to all patients in September 2000 to obtain current disease status and outcome information. Of 195 patients seen at the Mayo Clinic for PTM during this period, 178 were diagnosed for the first time at the Mayo Clinic between 1969 and 1995. (The remaining 17 patients had been diagnosed at this institution earlier.) The focus of this paper is the 178 patients with a new diagnosis in the study period.
Clinical criteria for diagnosis
Diagnosis of PTM was made in all patients by the presence of the typical clinical picture. The presentation included raised, waxy lesions of the skin, usually in the pretibial area. The lesions were usually light colored but could be flesh colored or yellowish brown. Hyperpigmentation and hyperkeratosis were also present in some cases, as was hyperhidrosis. The lesions were occasionally indurated and the hair follicles prominent so that the lesions had an orange peel (peau d’orange) or pig skin appearance and texture. Dermopathy was classified into one of the following four forms: nonpitting edema accompanied by typical skin color changes, plaque, nodular, or elephantiasic (Fig. 1
) (1). Endocrinologists usually performed the initial evaluation. More severe cases and cases requiring confirmation were referred to dermatologists.
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Histologic criteria for dermopathy (Fig. 2)
Histologic confirmation was obtained by punch biopsy specimens and hematoxylin and eosin and alcian blue-periodic acid-Schiff staining in 62.3% of the patients. Classic histopathologic features were seen, consisting of normal collagen in the papillary dermis and separation of the collagen bundles by mucin. Mucin staining demonstrated abundant diffuse mucin within the dermal fenestrations as large amounts of glycosaminoglycans (GAG) diffusely dispersed in the reticular part of the dermis. Although there was infiltration of lymphocytes in the perivascular space and mast cells were moderately increased in number in thyroid dermopathy, lymphocytic infiltration because of extensive GAG accumulation and edema was not seen in all biopsy specimens and was not a criterion for diagnosis.
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Diagnosis of hyperthyroidism and hypothyroidism was made by routine thyroid function tests, including measurement of TSH, serum-free T4, and total-serum T4. Thyroid-stimulating immunoglobulin was measured in some patients who were seen after 1985 (5%) by a method based on cAMP generation and was positive in all tested patients (1). The number of patients was not adequate to evaluate the effect of the level of thyroid-stimulating immunoglobulin on outcome of dermopathy.
Topical therapy
Topical treatment was initiated in the dermatology department, usually after histologic confirmation. Mild cases and cases without cosmetic or local functional problems were usually followed by endocrinologists, and topical therapy was not initiated. Patients who received therapy were generally treated with topical corticosteroids under occlusion or compressive dressings. The applied treatment was nighttime dressing of 0.05% to 0.1% triamcinolone acetate in cream base under occlusion with plastic film (Saran Wrap, Dow Chemical Co.). In some cases the cream was applied three times daily. Each course of therapy usually lasted 2–10 wk. Therapy was continued or repeated for longer periods, depending on clinical response (1). Compression was used in some patients and consisted of athletic wraps or compression stockings, providing 20–40 mm Hg pressure.
Evaluation of outcome
Complete remission was defined as absence of clinical dermopathy, and mild improvement or partial remission was defined as flattening of a plaque or nodule or reduction of edema. No improvement was defined as worsening of clinical dermopathy or no change in the appearance of the dermopathy. If the last relevant follow-up occurred at the patient’s last Mayo Clinic visit, the patient’s dermopathy was classified as absent, improved, unchanged, or worse on the basis of the physician’s documentation. The patient’s thyroid function status was noted as euthyroid on no therapy, euthyroid on thyroid replacement, hypothyroid, or hyperthyroid.
Patient questionnaire
The patients were asked whether their thyroid-related skin condition had returned entirely to normal (complete remission) or almost normal (mild improvement or partial remission), was unchanged, or was worse (no improvement). They were also asked whether they had received any treatment for PTM (local corticosteroid cream, oral corticosteroid, cosmetic surgery, or other) since their last visit to the Mayo Clinic. They were asked as well whether they had any skin problems in the legs (including cosmetic concern, local discomfort, and difficulty in wearing shoes or socks). Patients were also asked to indicate whether they were taking thyroid hormone replacement therapy.
Of the 178 patients in the study, 40 were deceased at the time of survey follow-up. Of the remaining 138 patients, 110 returned surveys (80% response rate), 3 refused participation, 14 could not be contacted, and 11 had no response or had other exclusions.
Statistical methods
Descriptive statistics, such as the mean and SD for continuous variables and frequencies for categorical variables, were computed. Baseline characteristics were compared among different groups with the chi-square test or two-sample t test when appropriate. When there were small numbers of patients in certain groups, Fisher’s exact test or the rank-sum test was used in lieu of the chi-square or two-sample t test.
Logistic regression analysis was used to determine predictors of outcome status. Because the severity of the disease was believed to be different in patients who received treatment, compared with those who did not, univariate and multivariate logistic regression models were computed separately for each of these two groups. The odds ratio (OR) and 95% confidence interval for the OR were computed. Expected time until mild improvement (partial remission) or complete remission was estimated using the Kaplan-Meier method.
All tests were two sided, and a P value of less than 0.05 was considered statistically significant.
Results
Demographics
Of 178 patients, 36 (20.2%) were men and 142 (79.8%) women. The mean age at diagnosis of PTM was 53.1 yr (range 14.3–79.6 yr). The average age for female patients was 52.9 yr (range 14.3–79.6) and for male patients 54.1 yr (range 31.8–75.7 yr). One hundred sixty-two patients (91.0%) were classified as hyperthyroid, seven (3.9%) hypothyroid, and five (2.8%) euthyroid; four (2.2%) were hypothyroid and then became hyperthyroid during follow-up. At last known follow-up, 40 (22.5%) patients had died.
Therapy of thyroid dysfunction
Of the entire group, 110 patients (61.8%) received one treatment with 131I, 43 patients (24.2%) had two treatments with 131I, 18 (10.1%) received 3 or more such treatments, and 7 patients (3.9%) did not receive any 131I treatments. Twenty-seven patients (15.2%) had undergone thyroidectomy. Forty-two patients (23.6%) had been treated with a single course of antithyroid agents, and one patient with 2 courses.
At last known status, 18 patients (10.1%) were euthyroid on no therapy, 135 (75.8%) were euthyroid on T4 therapy, 7 (3.9%) were hypothyroid, and 14 (7.9%) were hyperthyroid; the status of four patients was unknown. Including follow-up information obtained from the survey, the average follow-up was 14 yr (median 12.5 yr) from the time of diagnosis of thyroid dysfunction.
Other systemic manifestations of Graves’ disease
Most patients (83.1%) were diagnosed with thyroid disease before the diagnosis of dermopathy. Only five patients (3%) did not have any clinical evidence or history of ophthalmopathy. The remaining patients had significant eye disease at the time of diagnosis of dermopathy. Mild ophthalmopathy was present in 41%, moderate in 31%, and severe in 15.2%; optic neuropathy was present in 9.4% of the patients with dermopathy. Additionally, the majority of patients (71.9%) were diagnosed with ophthalmopathy before dermopathy. There was a high rate of rehabilitative eye surgery in the cohort, which included 46 eye muscle, 26 eyelid, 44 transantral orbital decompression, and 3 transfrontal decompression operations. Some required more than one corrective operation.
Thirty-one cases of acropachy were diagnosed (17.4%). With the available information, it was not possible to assess the outcome of acropachy.
Thyroid dermopathy
One hundred twenty-nine patients (72.5%) were first diagnosed with PTM at our institution. The remaining 49 patients were referred to our clinic with this diagnosis. Histologic confirmation of diagnosis was available in 104 patients (58.4%). The area of skin involvement was pretibial in 166 (93.3%), pretibial and feet in 7 (3.9%), pretibial and upper extremities in 2 (1.1%), and not documented in 1 patient. The clinical form of PTM was nonpitting edema in 77 (43.3%), plaque in 48 (27.0%), nodular in 33 (18.5%), elephantiasic in 5 (2.8%), and unclassifiable and/or unknown in 15 (8.4%). Endocrinologists usually made the initial diagnosis, and 116 patients (65.2%) received diagnostic confirmation by a dermatologist.
Initial treatment of thyroid dermopathy
Seventy-two patients (40.4%) received no specific therapy for their thyroid dermopathy, and 96 patients (53.9%) were treated by topical corticosteroids alone or in combination with other treatments. In 81.0% of those treated by topical corticosteroids, the agents were applied under occlusion. Only six patients received local corticosteroid injections, and one patient underwent surgical excision.
Baseline characteristics of the treated and untreated groups were different in the frequency of extreme forms of dermopathy, such as the elephantiasic form, which was present only in the treated group. The treated group also had more dermatologic referrals, which resulted in a higher rate of biopsy confirmation (P < 0.001). Treated patients were diagnosed with PTM later after the diagnosis of hyperthyroidism (P = 0.04) (Table 1). Patients who were treated were slightly older and were more likely to be male, although neither variable approached statistical significance (Table 1).
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Subsequent therapy and long-term follow-up of thyroid dermopathy (Tables 2 and 3)
The average length of follow-up for dermopathy was 7.9 yr (range 0–30.4 yr, median 5.4 yr), with follow-up ending at patient death, complete remission, or the patient’s last known follow-up (with a Mayo Clinic physician or by questionnaire). Eighty-two (46.1%) of the 178 patients did not receive any topical corticosteroid treatments, 81 (45.5%) received one course of treatment, 12 (6.7%) received two courses, and 3 (1.7%) received three or more courses. Duration of corticosteroid therapy was quite variable, the shortest duration being 5 d and the longest 8 yr. The majority had therapy for less than 1.5 yr; however, one patient reported using continuous local therapy for 2.3 yr and another for 8 yr. Of the 96 patients who received topical corticosteroid treatments, 50 (52.1%) had no or minimal improvement at last known follow-up (17 have since died), 26 (27.1%) had moderate improvement (six have since died), and 20 (20.8%) had complete remission (three have since died). Twenty-one patients (11.8%) received compressive dressing treatment. Of these, 14 received topical steroid therapy at some time (before, after, or simultaneously with the compressive dressings). Eleven patients received local corticosteroid injection (Tables 2 and 3). Nine patients received systemic corticosteroids for treatment of severe dermopathy.
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Using the Kaplan-Meier estimate, a 50% complete remission rate was achieved after 17 yr in patients who were untreated, but only 27% of patients treated with any treatment had complete remission at that point (Fig. 3). When partial remission and complete remission rates were combined, at 17-yr follow-up, 60% of the untreated group had partial or complete remission (Fig. 4), whereas the rate for the treated group was 50%. Patients who were not treated had a higher rate of complete remission than did treated patients (P = 0.03). No statistically significant difference was found between treated and untreated groups in the proportion of patients having combined complete plus partial remission (P = 0.30) as their final outcome.
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) and for patients who never received any treatment (Table 5). Of patients who received treatment at any time, those with a longer follow-up (OR = 1.04, P < 0.037), those who had transantral orbital decompression surgery (OR = 2.97, P < 0.01) and those who had eye surgery for Graves’ eye disease other than transantral orbital decompression surgery (OR = 2.51, P < 0.02) all had a significantly better final outcome. Hyperthyroid patients had worse (OR = 0.26, P < 0.03) final outcome than did patients who were not hyperthyroid. Although the difference is not statistically significant, patients who received corticosteroid therapy, local (OR = 2.18, P < 0.27) or systemic (OR = 1.27, P < 0.6), had a better final outcome than those who received other treatment for dermopathy. In a multivariate logistic regression analysis using a stepwise selection procedure, the only predictor of improved outcome in the treatment group was a history of transantral orbital decompression and eye muscle surgery for ophthalmopathy (Table 4).
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Discussion
Cause of thyroid dermopathy
About 0.5–4.3% of patients with a history of thyrotoxicosis have thyroid dermopathy, and 15% of patients with severe Graves’ ophthalmopathy have this cutaneous manifestation (2). The hallmark finding on biopsy specimens from these skin lesions is increased levels of GAG in the reticular, but not the papillary, dermis (2), with hyaluronic acid concentrations often 6 to 16 times higher in these lesions than in normal skin (10). This increased deposition apparently results from increased fibroblast stimulation, but the cause of this stimulation, although of autoimmune origin, is not yet clear.
It has been speculated that the thyroid-stimulating hormone receptor antibody plays a role (11, 12). Heat shock protein (13), IL-1, and TGF-ß (14) have also been implicated in PTM, although their roles are not clearly defined. Whatever the cause of the increased GAG production, accumulation of GAG leads to the characteristic skin lesions associated with thyroid dermopathy. Specifically, the hyaluronic acid expands the dermal tissue and causes fluid to accumulate. It may also cause compression or occlusion of small local lymphatics and thereby increase the dermal edema (4). These manifestations, as mentioned previously, are most commonly found in the pretibial area, a fact that several researchers have attempted to explain. Schermer et al. (15) suggested that the stasis of venous blood and the daily physical trauma to the lower extremities might stimulate mucin deposition. Rapoport et al. (16) also proposed that dependent edema may play a role, causing the slower return of lymph from the lower legs and increasing the half-life of fibroblast-stimulating cytokines locally. Other research indicates that fibroblasts in different regions of the body may have different characteristics and mechanisms of regulation (10).
However, other evidence suggests that deposition of GAG may not be just a local phenomenon. Wortsman et al. (17) found, on the basis of preradial skin biopsies, that preradial GAG deposition might occur commonly in patients with Graves’ disease, although this result was not found in another study (18). Salvi et al. (19), using ultrasonography, found increased pretibial skin thickness in 33% of patients with autoimmune thyroid disease, suggesting that dermopathy may be much more prevalent at the subclinical level than is diagnosed. Thus, increased deposition of GAG may occur throughout the body without clinical manifestations. The association of Graves’ disease with collagen disorders or markers of collagen disorders, including elevated levels of antinuclear antibody, supports the theory that connective tissue may be involved systemically as part of the autoimmune disease (20). The discovery of increased urinary GAG levels in patients with Graves’ disease also fits with this paradigm (21). Thus, the skin of the entire body may have a propensity to develop localized myxedema, but this only appears clinically in regions with additional mechanical (gravitational forces) or anatomic (site-specific differences in fibroblasts) factors. In fact, localized myxedema has been documented outside the pretibial region. Cases have been reported involving the shoulders, upper back, upper extremities, and pinnae (22). In our study, two patients had dermopathy of the upper extremities. When dermopathy occurs in these unusual locations, there is often a history of trauma.
Though the causes of dermopathy are debated, its development follows a predictable pattern. Generally, thyrotoxicosis develops first, followed by ophthalmopathy and finally dermopathy in patients who have all of these manifestations (1, 23). The results of our study were consistent with this pattern, with 83% of patients having had thyroid disease before the development of dermopathy and 72% having had ophthalmopathy before PTM. In 17%, thyroid acropachy was diagnosed, involving soft tissue swelling of the hands and feet with characteristic radiographic features (1, 5). In this study and in our previous report, almost 80% of the patient population were women and more than 90% of patients were hyperthyroid. Nonpitting edema was the most frequent form of dermopathy. In the present study, 3% of our patients did not have a diagnosis of clinical ophthalmopathy. A diagnosis of PTM in the absence of ophthalmopathy is always questionable. However, some of these patients may have had mild eye disease at an earlier time that was never diagnosed.
Pretibial myxedema has several typical clinical appearances. Nonpitting edema is the most common. This too was confirmed by the present study. However, raised plaques and nodules also often occurred in our patients. Rarely, patients present with an elephantiasic form consisting of nodules and lymphedema, five patients having had this extreme form in the present study.
Therapy of thyroid dermopathy
The treatment of dermopathy is usually symptomatic. Generally, PTM is only of cosmetic concern, but a case of peroneal nerve trapping has been reported (24), and associated lower extremity swelling can make shoes difficult to wear. In our study, 10 patients had such a problem, and 21 complained of local discomfort.
Local therapies. Therapy for thyroid dermopathy has variable success. Given the relatively benign nature of this problem, topical corticosteroids are more likely to be used than systemic therapy (1). Strengths of topical corticosteroids range from midpotency steroids, such as fluocinolone acetonide (3), to high-potency steroids, such as clobetasole propionate (25). Topical corticosteroids have had their absorption further enhanced with hydrocolloid (25) or plastic wrap occlusive dressings. Duration of these treatments varies. In general, occlusion is applied for at least 12 h each day. A trial of 4–6 wk may be reasonable but must be followed carefully to watch for signs of adverse effects from the topical steroids (e.g. atrophy, telangiectasis, and ecchymoses). Additionally, compression has been useful, especially when lymphatic involvement is suspected (4, 5). Ideally, compression consists of athletic wraps or compression stockings, providing 20–40 mm Hg pressure.
In a study by Kriss et al. (3), all 11 patients treated with 0.2% fluocinolone acetonide cream under occlusion experienced "favorable dermatologic responses" within 4–6 wk, but attempts at achieving long-term remission were unsuccessful because of undesirable side effects. However, it is unclear whether this favorable response corresponds to the "partial remission" classification used in our study. In our study, we had a 47.9% partial or complete remission rate among more severe cases treated with corticosteroids at any time, compared with a 55.6% partial or complete remission rate among patients with milder disease who did not receive any treatment. Patients with more severe dermopathy are more likely to receive local corticosteroids, whereas patients with mild disease are more likely to receive no treatment at all. The long-term outcome appears to be better in milder cases despite the absence of therapy.
Twelve percent of our patients received compressive dressings in combination with local corticosteroids. The 23.8% complete remission rate in these patients exceeds that with use of topical corticosteroids alone.
In addition, intralesional octreotide injection has recently shown promise in the treatment of PTM but needs further study (26, 27). No patients in our study underwent this therapy. Surgical excision (28) has been reported. However, surgical intervention is not advised because of the high rates of recurrence (29). Intralesional corticosteroids, such as triamcinolone acetonide, have also been used with some success (7). The use of intralesional steroid injections is losing favor, despite a few favorable reports (6, 7), because of their tendency to cause lumpy-appearing skin and the frequent recurrence of disease after treatment (2, 7). Only 6.2% of patients in our study received corticosteroid injections; their remission rate was 27.3%, greater than that for patients receiving topical corticosteroids or compressive dressings. However, since some patients received more than one mode of therapy, additional benefits from local corticoid injection cannot be determined.
Systemic immunomodulatory therapy. Immunomodulation such as systemic corticosteroids (30) and cytotoxic therapy (31) have also produced improvement in patients with PTM, but because of their side effects these agents are rarely used unless required for therapy of associated ophthalmopathy. High-dose iv immunoglobulin treatment (32) and plasmapheresis (33, 34) have also been used to treat PTM in a few patients and have led to improvement or remission of the condition (33).
Outcome of local therapy.
In our previous report (1), involving fewer patients and a shorter follow-up, we found that 38% of patients experienced partial remission of their dermopathy and only 8% had complete remission. However, in the present study with longer follow-up, 24% had partial remission and 26% complete remission. This result suggests that with longer follow-up more patients will experience complete remission of their dermopathy. In fact, the untreated patients with 17 yr of follow-up had a 50% complete remission rate (Fig. 3
).
There was no statistically significant difference in complete plus partial remission rate between the local therapy and the no-therapy groups. The trend of better outcome in the untreated group is likely related to the severity of the cases of dermopathy, those with more severe disease receiving treatment more often than those with milder dermopathy. Combined partial or complete remission rate gradually increased with time, to 70% in the group with no treatment and 58% in the treated group 25 yr after the diagnosis of PTM (Fig. 4). Patients with more severe dermopathy would logically be expected to have a lower rate of complete remission than those with milder disease. Thus, if patients with severe dermopathy are those receiving topical corticosteroids, compressive dressings, or intralesional corticosteroid injections, the long-term efficacy of these treatments is difficult to evaluate from the present study because they cannot be compared with the no-therapy group.
Conclusion and recommendations
The present study supplies information about the natural course of treated and untreated thyroid dermopathy, but there are some limitations. The treated and untreated groups were not comparable. Half of patients with thyroid dermopathy experienced significant improvement or complete disappearance of PTM lesions after long-term follow-up. The difference in outcome, in terms of combined complete and partial remission, between treated severe cases and nontreated mild cases was not significant, but the nontreated mild group had a tendency for better outcome. This could be related to the severity of the treated cases, and we cannot conclude that treatment in severe cases does not improve long-term outcome. Although the previous and present reports suggest short-term benefits from topical corticosteroid therapy in thyroid dermopathy, the effect of short-term initial topical therapy on long-term benefits remains to be determined. For a definitive conclusion, randomized clinical trials may be necessary to determine which treatments for thyroid dermopathy promote long-term remission. But such long-term randomized trials may not be feasible because of the rarity of the condition. Short-term study may not be indicative of long-term results because of the occurrence of remission often years after termination of therapy. Meanwhile, to achieve better outcomes, new modes of therapy are needed.
At present, immunomodulation such as with systemic corticosteroid therapy, iv Ig, and octreotide are used for severe cases of Graves’ ophthalmopathy (9). This therapy, directed at ophthalmopathy, is likely to result in improvement of associated dermopathy. For these patients, local corticosteroid therapy under occlusion may offer additional help. If there is edema, especially in elephantiasic cases, compression can be added to local corticosteroid therapy. Mild cases of dermopathy can be observed, or they can be treated with local corticosteroids if there is cosmetic concern or local discomfort. Optimum local corticosteroid therapy is usually 4–8 wk and can be extended to 1 yr, depending on response. Trauma to dependent and other areas of skin should be avoided. Surgical excision is not recommended, and local corticosteroid injection is not advised at the present time. Evidence for benefits of systemic or local octreotide therapy is inadequate.
Footnotes
This work was supported in part by the Richard F. Emslander Clinical Investigator Award. K.M.S. is a student at Mayo Medical School.
Abbreviations: GAG, Glycosaminoglycans; OR, odds ratio; PTM, pretibial myxedema.
Received June 3, 2001.
Accepted October 29, 2001.
References
This article has been cited by other articles:
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  V. H. Prajapati and P. R. Mydlarski Answer: Can you identify this condition? Can Fam Physician, March 1, 2008; 54(3): 369 - 369. [Full Text] [PDF]
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 V. Fatourechi, D. D. F. Ahmed, and K. M. Schwartz Thyroid Acropachy: Report of 40 Patients Treated at a Single Institution in a 26-Year Period J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5435 - 5441. [Abstract] [Full Text] [PDF]
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