Necrobiosis lipoidica (NL) is an idiopathic inflammatory skin disorder that rarely resolves spontaneously, and ulceration is a major complication. Although NL occurs in less than 1% of patients with diabetes mellitus, 75% of NL cases are associated with diabetes.1
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency encountered in adults: incidence is estimated at between 1 in 10 000 and 1 in 50 000. Because of the heterogeneity of this disorder, no targeted therapy has been defined except intravenous immunoglobulin (IVIG).2 Herein, we describe a patient with diabetes who experienced a successful combined treatment of NL ulcers and CVID with IVIG.
A 63-year-old white woman with diabetes was referred to us with a 7-year history of ulcerating and very painful NL lesions on her shins, which had gradually enlarged during this period. The patient was a smoker and had a history of well-controlled type 2 insulin-treated diabetes mellitus (hemoglobin A1c proportion, 6.1%) with no additional diabetic complication. Physical examination revealed atrophic, yellow-brown, telangiectatic plaques affecting her lower legs. The lesions had large, deep, and crusting ulcerations (Figure 1). Cutaneous biopsy findings were compatible with NL, and direct immunofluorescence findings were negative. The patient had previously received treatments with topical corticosteroid, topical tacrolimus, hydroxychloroquine, psoralen plus UV-A, and pentoxifylline without any significant clinical response. Owing to recurring ear, nose, and throat infections, CVID was suspected. Immunologic tests revealed a poor response to vaccines (pneumococcus and diphtheria) and reduced serum immunoglobulin concentrations (IgG, IgM, and IgA at 77, 23, and 40 mg/dL, respectively). No secondary cause of hypogammaglobulinemia was observed (no history of immunosuppressive therapy, digestive symptoms of inflammatory disease, nor evidence for neoplasia by thoraco-abdominal computed tomographic scan and flow cytometry).
Lower pretibial right (A) and left (B) legs before intravenous immunoglobulin therapy showing large and ulcerative plaques of necrobiosis lipoidica.
The patient was subsequently treated with IVIG, 0.4g/kg/d, for 5 consecutive days for her newly diagnosed CVID, while local application of paraffin gauze dressing (Jelonet; Smith & Nephew) was maintained. Surprisingly, 3 weeks after this single cycle, all ulcerations had healed (Figure 2), and complete resolution of pain was reported. The immunoglobulin levels remained stable 3 months after IVIG treatment, and no further ulcerations were detected during a 2-year follow-up, and so the patient did not require additional therapy.
Lower pretibial aspect of the legs after Intravenous Immunoglobulin therapy showing substantial healing.
In our case, no significant success was observed in reduction of NL ulcers after administration of currently accepted treatments, the efficiency of which was known to be limited. Interestingly, treatment of the patient’s CVID with IVIG appeared to heal the ulcers within 3 weeks. As the IVIG treatment showed a similar dramatic ulcer reduction within 2 weeks in a previous case3 (where no investigation of associated hypogammaglobulinemia was performed), the immunologic aspect of NL appears of major importance in these patients. Because of its strong association with diabetes, NL has been postulated to arise due to microangiopathic vascular changes. Therefore, NL might be due to immunologically mediated vascular changes.4,5 In this context, measures of serum immunoglobulin levels and direct immunofluorescent histologic study might be recommended in NL.
Our findings suggest that IVIG can be a successful option in the treatment of NL, particularly in patients with CVID, while a broader approach in NL without underlying CVID requires further investigations.
Corresponding Author: Neda Barouti, MD, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland (email@example.com).
Conflict of Interests Disclosures: None reported.
Funding/Support: This study was supported by the University Hospitals of Geneva, Geneva, Switzerland.
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript.
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