Necrobiosis lipoidica diabeticorum
Necrobiosis lipoidica diabeticorum is a rare, chronic, idiopathic disorder of collagen degeneration with a granulomatous response, thickening of blood vessel walls, and fat deposition. In 1929, it was first described by Oppehhein, as dermatitis atrophicans lipoidica diabetica. In 1932, Urbach renamed the disease as necrobiosis lipoidica diabeticorum (NLD). It is associated with the risk of ulceration and classically associated with diabetes mellitus, usually, type 1 and affects 0.3% of diabetic patients. The increased prevalence in diabetic individuals is currently questioned. Necrobiosis lipoidica precedes diabetes in up to 14% and appears simultaneously in up to 24% and occurs after diabetes is diagnosed in 62% of cases. Also, no connection has been proved between the level of glycemic control and the likelihood of developing necrobiosis lipoidica.
The common sites for NLD are legs, abdomen, upper extremities, and scalp. The etiology and pathogenesis of NLD are still controversial, it is thought that microangiopathy has an important role. It is more often seen in women with a predominance of 77%. Although it may present in healthy individuals with no underlying disease, other commonly associated conditions are thyroid disorders and inflammatory diseases, such as Crohn disease, ulcerative colitis, rheumatoid arthritis, and sarcoidosis. Few studies are suggestive of both hyperlipidemia and venous reflux, in addition to other pathogenic factors, which trigger tissue damage in the lower legs whereas others conclude that the increased blood flow seen in NLD lesions are suggestive of an ongoing inflammatory process. Histopathologically NLD is characterized by interstitial and palisaded granulomas that involve the subcutaneous tissue and dermis. The granulomas which are composed of histiocyte are arranged in a tier fashion and are admixed with areas of collagen degeneration. Some of them are multinucleated lymphocytes, occasional plasma cells, and eosinophils.
Reduction in the number of the intradermal nerve is an additional feature of NLD. The main findings on histopathology are thickening of the blood vessel walls and endothelial cell swelling found in the middle to deep dermis, the characteristics shared with diabetic microangiopathy. Biopsy in few patients has revealed sandwich-like horizontal layers of necrobiotic collagen alternating with inflammatory cell infiltrate of lymphocytes, histiocytes, multinucleated giant cells, and plasma cells. Direct immunofluorescence microscopy of NLD has demonstrated vascular thickening due to IgM, IgA, C3, and fibrinogen in the blood vessels. In nondiabetic subjects, the vascular changes are not that prominent.
There is no rational therapy for the disease. There are plenty of therapeutic options available for NLD but its treatment is still challenging and sometimes ineffective. First-line treatment includes corticosteroids, either topically or intralesionally, and sometimes systemically. Other studies recommend smoking cessation and blood glucose control. Some more therapeutic options are the use of antiplatelet agents, cyclosporine, thalidomide, clofazimine, anti-TNF agents, fumaric acid esters, photodynamic therapy, hydroxychloroquine, and tacrolimus. Tacrolimus induces suppression of the granulomatous infiltrate including the reduction of chemotactic activity of fibroblasts and the inhibition of collagen synthesis, anti-inflammatory, and immunomodulatory effects. Subsequently, tacrolimus is thought to be effective at the early inflammatory stages of NL. Significant insights have been made into its pathophysiology and treatment of NLD even though its details are still elusive. We are spoilt for choice of treatment options that are there in our pharmacological armory to fight with this benign devil which accompanies diabetes.