CASE RECORDS OF THE VUK VRHOVAC UNIVERSITY CLINIC

Spomenka Ljubic, Nikica Car, Ivana Pavlic-Renar, Zeljko Metelko

Vuk Vrhovac Institute, University Clinic for Diabetes, Endocrinology and Metabolic Diseases,
Dugi dol 4a, 10000 Zagreb, Croatia

Case Report

Received: June 7, 1999

CASE PRESENTATION

A 48-year-old man was admitted to the hospital for glycemic control and evaluation of late complications of diabetes mellitus. Care was focused on skin lesions of both pretibial areas (Fig. 1).

Figure 1. Lower leg skin lesions in our patient with diabetes mellitus


Figure 1

Clinical diagnosis was necrobiosis lipoidica. Until then, the patient had suffered no diseases except for an operation of the right leg ten years before because of variceal bleeding. Diabetes mellitus had been diagnosed two years before, and the patient was receiving an oral hypoglycemic agent, gliquidone. On admission, he was on one tablet of gliquidone in the morning. He was not on diet, and reported a weight loss of 12 kg over the past two years. The patient's blood pressure was 130/90 mm Hg, body temperature 36.4 °C, pulse 86, and he reported no problems with his appetite, stool or urination. There was no history of smoking or alcohol ingestion. The results of physical examination were normal, with the exception of some areas of atrophic hyperpigmented skin on both pretibial regions and swelling of the right lower leg. Laboratory test results showed considerable elevation of glycemia and glycated hemoglobin (HbA1c, 16.46%), and slight elevation of the blood leukocyte count, total cholesterol and LDL-cholesterol. Radiography showed hilar enlargement. Funduscopy pointed to nonproliferative retinopathy and maculopathy bilaterally. Neurologic examination indicated mild polyneuropathy.
As mentioned above, attention was focused on skin lesions, thus skin biopsy was performed. The pathohistologic finding pointed to the diagnosis of granuloma annulare. The biopsy material was also submitted to direct immunofluorescent test (DIF). IgA± deposits, C3++, C1q(+) and fibrinogen were found in the blood vessels of the corium.

DISCUSSION

Granuloma annulare and necrobiosis lipoidica are cutaneous lesions that share certain clinical and pathologic features, and may occur simultaneously in patients with diabetes mellitus. Their occurrence used to be primarily related to diabetes mellitus, however, recent studies have pointed to their association with many systemic diseases, i.e. they are considered as one of their external manifestations (1,2). Sarcoidosis, autoimmune thyroiditis, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, Wegener's granulomatosis, Churg and Strauss granulomatosis, have been mentioned, with the accent placed on their association with rheumatoid arthritis (3). Some studies point to viral infection as the cause of immune complex-mediated immune reaction, i.e. immune vasculitis might be involved in the pathogenesis of these lesions (4,5). Cytomegalovirus, adenovirus, and Epstein-Barr virus have been mentioned as the possible pathogens. In systemic diseases as well as in viral infections, the vasculitic component in the development of such lesions should not be neglected (3).
In our patient, histology with special staining (toluidine) revealed collagen tissue degeneration, with lymphocytes and histiocytes palisading along the border. The finding of mucin corresponded to the histologic feature of granuloma annulare (1,6). The DIF finding might correspond to leukocytoclastic vasculitis, however, typical leukocytes for this clinical entity have not been described (5,7,8). It should be noted that a different DIF finding could have been due to the presence of chronic lesions in our patient. There were varices on his lower legs, which may cause atrophy and hyperpigmentation of the skin due to their tendency to ulceration.

Data on previous infections, rash, fever, arthralgias or diarrheas could be very useful. The patient's weight loss should needs an explanation, to find out whether it was simply consequential to glycemia control. The patient should be instructed to present to the hospital in case of the occurrence of such symptoms, because of the importance of thorough examination and appropriate therapy. Serologic testing for the above mentioned viruses, and determination of total C, C3, C4, CIC, CRP, IgM, IgG, IgA, AST and ASTA, as well as of hematologic parameters such as erythrocyte sedimentaion rate (ESR), could be very useful in the diagnostic procedure. If symptoms of any systemic disease are observed, immunologic tests pointing to the suspected disease should be performed.

Concerning therapy, an improvement in the glycemia control during hospitalization was achieved with four tablets of glibenclamide. The patient had no signs of nephropathy, and this hypoglycemic agent was a justified substitution for the previously used gliquidone. With respect to the patient's age, insulin therapy should be considered if the increased levels of glycemia and HbA1c persist on his next visits to the Clinic. Based on the previous studies, local application of corticosteroids and balneophotochemotherapy for skin lesions are recommended (9). A corticosteroid, methylprednisolone, 0.5 mg/kg, with a 10% dose reduction every 7 days, is the treatment of choice for vasculitis. Due to its side effects, immunoglobulin therapy is still under discussion. In addition, appropriate therapy should be introduced for any systemic disease that may possibly be diagnosed in the patient. If the lipid increase persists even after good glycemia control has been achieved, an appropriate hypolipemic agent will be administered. The levels of transferases should be controlled every 2-3 months at the beginning of therapy, because of the possible side effects. The right leg swelling may have been caused by deep venous thrombosis. The diagnostic procedure should include duplex Doppler sonography. Late complications such as ophthalmologic and neurologic ones require regular and continuous supervision.
In conclusion, granuloma annulare and necrobiosis lipoidica belong to external manifestations of systemic diseases including diabetes mellitus. In the treatment of granuloma annulare and necrobiosis lipoidica, accent should be placed on appropriate therapy for the underlying systemic disease(s).

REFERENCES

  1. Magro CM, Crowson AN, Regauer S. Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation of systemic disease. Hum Pathol 1996;27:50-56.
  2. Papadopoulos KI, Hörnblad Y, Liljebladh H, et al. High frequency of endocrine autoimmunity in patients with sarcoidosis. Eur J Endocrinol 1996;134:331-336.
  3. Person JR. Generalized granuloma annulare, mononucleosis, and positive rheumatoid factor. Int J Dermatol 1995;34:40-41.
  4. Ledford DK. Autoimmune disease, serologic testing, and immune complex assessment. J Allergy Clin Immunol 1989;84:1082-1094.
  5. American College of Rheumatology Subcommittee on Classification of Vasculitis. The American College of Rheumatology 1990 Criteria for the Classification of Vasculitis. Arthritis Rheum 1990;33:1065-1079.
  6. Fölster-Holst R, Kiene P, Christophers E. Ungewönliche zirzinäre Variante eines generalisierten Granuloma annulare. Hautarzt 1996;47:53-57.
  7. Mitchel BA, Hunder GG, Bloch DA, et al. Hypersensitivity vasculitis and Henoch-Schönlein purpura: a comparison between the two disorders. J Rheumatol 1992;19:721-728.
  8. Jenette JC, Falk RJ, Androssi K, et al. Nomenclature of systemic vasculitis: proposal of an international consensus conference. Arthritis Rheum 1994;37:187-192.
  9. Langrock A, Wejers W, Schill B. Balneophotochemotherapie bei disseminiertem Granuloma annulare. Hautarzt 1998;49:303-306.


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