Necrobiosis lipodica | DermNet

Author: Hon A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand, 2006. DermNet NZ Update August 2021

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What is necrobiosis lipoidica?

Necrobiosis lipoidica is a rare granulomatous skin disorder typically described on the shin of diabetics.

Necrobiosis lipoidica

Who gets necrobiosis lipoidica?

Necrobiosis lipoidica is three times more common in females than in males, and usually develops in young and middle-aged adults.

• 1% of patients with diabetes will develop necrobiosis lipoidica.
• It can occur in both type 1 and type 2 diabetes mellitus.
• 11–65% of patients with necrobiosis lipoidica have diabetes or prediabetes.
• Diabetes associated with necrobiosis lipoidica can be well controlled or poorly controlled.
• Patients with type 1 diabetes are more likely to be younger than those with type 2 diabetes or without diabetes.
• Other associations include obesity, hypertension, dyslipidaemia and thyroid disease.
• Necrobiosis lipoidica is rare in children.

What is the cause of necrobiosis lipoidica?

The cause of necrobiosis lipoidica is unknown. Theories have included blood vessel changes such as develop in diabetes, or antibody-mediated vasculitis.

What are the clinical features of necrobiosis lipoidica?

Necrobiosis lipoidica begins as a dull red papule or plaque on the shin which slowly enlarges into one or more yellowish-brown patches with a red rim.

The patches:

• Most often occur on both shins and are found in other sites only rarely
• May be asymptomatic or tender
• May be round, oval, or an irregular shape
• Central atrophy – shiny, pale, and thinned, with prominent blood vessels (telangiectasia)
• May demonstrate reduced sweating and sensation.

Dermoscopy of necrobiosis lipoidica

• Yellow structureless background
• Linear vessels with uniform branching
• White linear streaks

How does necrobiosis lipoidica present in differing skin types?

In skin of colour, the patches and plaques of necrobiosis lipoidica may be hyperpigmented around the periphery with hypopigmentation developing centrally with the atrophy and telangiectases.

What are the complications of necrobiosis lipoidica?

• Ulceration complicates 1/3 of cases of necrobiosis lipoidica, usually following minor injury to an established patch. The ulcer may be very painful or painless.
• Ulcers due to necrobiosis lipoidica are at risk of secondary bacterial infection and delayed healing.
• Squamous cell carcinoma has been reported to develop in ulcerated necrobiosis lipoidica.

Ulcerated necrobiosis lipoidica

What is the differential diagnosis of necrobiosis lipoidica?

• Actinic granuloma
• Necrobiotic xanthogranuloma
• Sarcoidosis

How is necrobiosis lipoidica diagnosed?

Necrobiosis lipoidica is diagnosed clinically when typical.

A skin biopsy may be performed to confirm the diagnosis. The histopathology is characteristic; it shows a granulomatous inflammatory reaction around destroyed collagen (necrobiosis). [see Necrobiosis lipoidica pathology].

What is the treatment for necrobiosis lipoidica?

Not all cases of necrobiosis lipoidica require treatment and treatment is generally disappointing. The following treatments are sometimes effective:

• Corticosteroids — topical or intralesional
• Topical tacrolimus
• Photochemotherapy (PUVA).

What is the outlook for necrobiosis lipoidica?

Necrobiosis lipoidica is a chronic condition that may remain stable or slowly progress over years. Spontaneous resolution has been reported.

Bibliography

• Peckruhn M, Tittelbach J, Elsner P. Update: treatment of necrobiosis lipoidica. J Dtsch Dermatol Ges. 2017;15(2):151–7. doi:10.1111/ddg.13186. Journal
• Shrestha S, Spierings N, Marahatta S. Necrobiosis lipoidica: a case report with dermoscopic review. Clin Case Rep. 2021;9(3):1171–4.  doi:10.1002/ccr3.3713. Journal 
• Uva L, Freitas J, Soares de Almeida L, et al. Squamous cell carcinoma arising in ulcerated necrobiosis lipoidica diabeticorum.  Int Wound J. 2015;12(6):741–3. doi:10.1111/iwj.12206. Journal
• Yahya H. Necrobiosis lipoidica in a Nigerian woman — report of a case. Niger J Clin Pract. 2019;22(11):1626–8. doi:10.4103/njcp.njcp_40_19. Journal

On DermNet NZ

• Necrobiosis lipoidica pathology
• Diabetic foot ulcers
• Granuloma annulare
• Skin signs and systemic disease

Other websites

• Necrobiosis lipoidica — emedicine dermatology ndash; Medscape Drugs & Diseases
• Necrobiosis Lipoidica — British Association of Dermatologists 

Books about skin diseases

• Books about the skin
• Dermatology Made Easy book

Successful Treatment of Necrobiosis Lipoidica Diabeticorum With Photodynamic Therapy | Dermatology | JAMA Dermatology

Report of a case

A 60-year-old white woman was seen at our clinic with a 10-year history of 4 asymptomatic progressive shiny patches on the right lower leg. The patient also had type 1 diabetes mellitus that was well controlled and had been so throughout the period; in addition to daily insulin, the only medication used was a nonsteroidal anti-inflammatory drug to treat symptoms of arthrosis. She had never received skin grafts; had no ulceration, deep venous thrombosis, or cellulitis; had never undergone a surgical procedure; and had never experienced trauma to the legs. The patches were initially red to brown, but 2 had progressed to yellow, slightly atrophic plaques, and 2 lesions had enlarged to a diameter of 5 to 6 cm with prominent red borders. Physical examination revealed annular, well-circumscribed erythematous plaques with waxy, telangiectatic centers and slightly elevated red borders. None of the lesions had ulcerated (Figure 1). Analysis of a biopsy specimen confirmed the diagnosis of necrobiosis lipoidica diabeticorum (NLD).

Figure 1. 

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Analysis of a pretreatment biopsy specimen verified the diagnosis of necrobiosis lipoidica diabeticorum. A, Gross view. B, Close-up view of the lesion.

Therapeutic challenge

Necrobiosis lipoidica belongs to the idiopathic cutaneous palisading granulomatous dermatitides associated with a degeneration of collagen, and is most often seen on the legs and often occurs in patients with diabetes mellitus. The disease may lead to skin atrophy, which may be aggravated by topical or intralesional treatment with corticosteroid agents, which constitute the most widely used therapy. Likewise, systemic glucocorticosteroid agents may induce skin vulnerability and elevated serum glucose levels, which contraindicated the use of this drug in our patient with diabetes. Alternatively, psoralen plus UV-A was considered usable, but because of risk of hyperpigmentation and bullous lesions, the patient declined this option.

Treatment with high-potency topical mometasone furoate 0.1% (Elocon; Schering Corp, Kenilworth, NJ) and clobetasol propionate (Dermovat; GlaxoSmithKline, Research Triangle Park, NC) and systemic antioxidant therapy with ascorbic acid and vitamin E for 6 months was ineffective. Likewise, cryotherapy, a series of radiotherapy using grenz rays, and a 3-month trial of systemic allopurinol therapy were discontinued because of lack of response.

Because successful treatment options for NLD seemed limited, we initiated a regimen of photodynamic therapy (PDT) using methyl aminolevulinate (Metvix; PhotoCure ASA, Oslo, Norway) as a topical photosensitizer and an incoherent red-light source. In a previously published study,¹ PDT appears to have an anti-inflammatory effect as well as a tissue-conserving effect.

Solution

Photodynamic therapy was initiated with 632 nm of red-light (CureLight 2; Photocure ASA; 37 J/cm² [light-emitting diodes, 580-670 nm], peak wavelength at 631 nm) activation of methyl aminolevulinate applied to the histologically verified NLD lesion. The procedure included application of methyl aminolevulinate (160 mg/g) under adhesive bandage occlusion for 3 hours to the NLD lesion before exposure to red light. The illumination was administered for 8 minutes and was tolerated without the use of local or systemic analgesia.

During 3 treatments given 1 week apart, a marked reduction in size and color of the lesion was noted, and after a further 3 treatments administered at the same intervals the lesion disappeared clinically and histologically (Figure 2). Findings at 24-month follow-up suggest an ongoing stabilized remission status.

Figure 2. 

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View of the same patient’s leg after 6 treatments with photodynamic therapy. A random biopsy specimen did not contain any remnants of necrobiosis lipoidica diabeticorum.

Comment

Necrobiosis lipoidica diabeticorum is a skin disease that is usually difficult to treat.^2-4 The evidence base of all therapy is limited.

One clinical trial, which tested the use of aspirin therapy, reported negative results.⁵ First-line therapy for NLD includes nonsteroidal inflammatory agents, cryotherapy, and potent topical glucocorticoid agents for early lesions and intralesional corticosteroids injected into the active borders of established lesions. Systemic glucocorticoid therapy may also be effective but can be associated with adverse effects in patients with diabetes. Other therapies for NLD are used in an attempt to decrease the microangiopathy and vascular thrombosis by increasing fibrinolysis or decreasing platelet aggregation and thromboxane A₂ synthesis. Anecdotal reports include uncontrolled NLD case series mention stanozolol, inositol niacinate, nicofuranose, ticlopidine hydrochloride, pentoxifylline, retinoids, cyclosporin, chloroquine, fumaric esters, psoralen plus UV-A, and allopurinol as treatment options^2-4,6,7; however, these treatments are only marginally effective in most patients. No major randomized controlled trials are available to identify best clinical practice.

Photodynamic therapy is mediated by oxygen-dependent photochemical reactions. On absorption of photons of light, the photosensitizer is excited to a short-lived singlet state followed by transition to the reactive triplet state. From its triplet state, in the presence of oxygen, reactive free radicals and singlet oxygen species ensue. These, in turn, react with cell membranes, causing direct damage to the mitochondria, endoplasmic reticula, or plasma membranes. Some indirect effects may also occur in the normal microvasculature and in the inflammatory and immune host system. The most common adverse effect of PDT is pain, burning, or stinging at the site of treatment, although most patients, like ours, do not request pain relief.

Photodynamic therapy is a well-established treatment mainly used for dermato-oncologic conditions.^1,8,9 By using noncoherent and coherent light sources on a photosensitizer, such as the heme precursor 5-aminolevulinic acid or its methyl ester (methyl aminolevulinate), to induce photosensitizing porphyrins, light and oxygen cause photochemical tissue destruction and immunomodulation. This suggests that the off-label use of PDT might be an effective treatment option for a range of inflammatory dermatoses, such as localized scleroderma, acne rosacea, and psoriasis. ^10-12 Photodynamic therapy has also been suggested for photorejuvenation of UV-light damaged skin.¹³

Necrobiosis lipoidica diabeticorum may undergo spontaneous remission with or without residual cutaneous atrophy and scarring, which develops over a longer period. Our patient had stable disease before PDT, with total regression of the lesions after initiation of PDT. Furthermore, regression occurred without atrophy and obvious scarring. This suggests that spontaneous remission was not a probable explanation for our observation.

The immunologic effects of PDT include the production of interleukin 1β, interleukin 2, tumor necrosis factor α, and granulocyte colony-stimulating factor. These factors may have a role in the inflammatory or metabolic changes in NLD, but the exact mechanism has yet to be elucidated.

Topical PDT using methyl aminolevulinate seems to offer a practical noninvasive therapy option for NLD conditions, with the potential for high efficacy and good cosmesis. However, controlled clinical trials are needed to demonstrate more fully the effectiveness of PDT in inflammatory skin diseases.

Submissions

Clinicians, residents, and fellows are invited to submit cases of challenges in management and therapeutics to this section. Cases should follow the established pattern. Manuscripts should be prepared double-spaced with right margins nonjustified. Pages should be numbered consecutively with the title page separated from the text (see Instructions for Authors for information about preparation of the title page). Clinical photographs, photomicrographs, and illustrations must be sharply focused and submitted as separate JPEG files with each file numbered with the figure number. Material must be accompanied by the required copyright transfer statement (see Instructions for Authors). Preliminary inquiries regarding submissions for this feature may be submitted to George J. Hruza, MD ([email protected]). Manuscripts should be submitted via our online manuscript submission and review system (http://manuscripts. archdermatol.com).

Correspondence: Michael Heidenheim, MD, Department of Dermatology, Roskilde Hospital, Koegevej 4-7, 4000 Roskilde, Denmark ([email protected]).

Financial Disclosure: Dr Jemec has lectured on photodynamic therapy and has received an honorarium for these lectures from PhotoCure ASA.

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Article Information

Accepted for Publication: April 28, 2006.

Author Contributions:Study concept and design: Heidenheim and Jemec. Acquisition of data: Heidenheim and Jemec. Analysis and interpretation of data: Heidenheim and Jemec. Drafting of the manuscript: Jemec. Critical revision of the manuscript for important intellectual content: Jemec. Administrative, technical, and material support: Heidenheim and Jemec.

References

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 RM Photodynamic therapy in dermatology: an update.   Photodermatol Photoimmunol Photomed 2005;21142- 149PubMedGoogle ScholarCrossref

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 et al.  Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study.  Br J Dermatol 2005;153802- 807PubMedGoogle ScholarCrossref

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 RM Topical photodynamic therapy for localized scleroderma.   Acta Derm Venereol 2000;8026- 27PubMedGoogle ScholarCrossref

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 NC Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts.  Lancet 2000;355963- 966PubMedGoogle ScholarCrossref

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 et al.  Improved response of plaque psoriasis after multiple treatments with topical 5-aminolaevulinic acid photodynamic therapy.  Acta Derm Venereol 1999;79451- 455PubMedGoogle ScholarCrossref

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Lipoid necrobiosis in patients with diabetes mellitus: pathogenetic and clinical features | Semenova

The etiology and pathogenesis of necrobiosis lipoidis (LN) have not been finally established. Factors contributing to the development of dermatosis are autonomic neuropathy, disorders of carbohydrate and lipid metabolism, immunological changes, and pathology of the microvasculature. The diagnosis is based on the results of clinical, biochemical and histological examination. The use of modern methods allows for the differential diagnosis of LN and other skin diseases, as well as the development of therapeutic tactics.

To date, there are no treatments for LN that have been proven effective in randomized, double-blind, controlled trials. The following areas of therapy can be distinguished: correction of disorders of carbohydrate metabolism and blood rheological properties, normalization of microcirculation parameters, anti-inflammatory therapy, surgical treatment, local wound treatment, immunomodulation. Research is aimed at finding optimal methods for treating LN.

Definition

LN is a relatively rare chronic vascular-exchange dermatosis, usually referred to the group of localized skin lipoidosis, characterized by the deposition of lipoids in those areas of the dermis where there is degeneration or necrobiosis of collagen [1].

History of study, terminology

The first description of LN was by Maurice Oppenheim in 1929. A patient demonstrated at a meeting of the Vienna Dermatological Society had lesions on the ventral and dorsal surfaces of the legs, trunk and face. Initially, the elements were papules, then nodular plaques. The disease was named dermatitis atrophicans lipoidica diabetica. At 1932 AD Erich Urbach describes a second case of “metabolic dermatosis” in a 44-year-old woman and renames it necrobiosis lipoidica, seudiabetic. Histological examination in the foci showed lipid deposition among collagen bundles, accumulation of lymphocytes and fibroblasts. Urbach believed that skin lesions are caused by a pathological change in the vessels of the dermis, which is associated with exposure to a hypothetical “diabetic toxin”. In Russia, LN was first described in 1940 by A.V. Ustinovsky. At 1960 T.G. Rollins and R.K. Winkelmann showed that dermatosis can also develop in patients without diabetes mellitus (DM), and therefore it was proposed to exclude the word “diabetic” from the name. To date, the term “necrobiosis lipoidica” is considered generally accepted, since it accurately reflects the essence of the morphological changes occurring in the lesions.

Epidemiology. Association with other diseases

To date, LN has ceased to be considered a casuistic rarity, and, starting from the 80s of the last century, it began to be registered in practice much more often. Apparently, this can be explained by the increase in the same years in the incidence of type 2 diabetes (DM2) in the general population. At present, the prevalence of DM has reached epidemic proportions: according to WHO, the number of patients is 285 million people, and in 2025 it is expected to reach 380 million people. In Russia, the registered prevalence of DM is about 1.5% of the adult population (while the actual prevalence of DM2 is 2-3 times higher than the registered one). In the structure of SD 80–95% are people with DM2. According to experts, about 200 million people have impaired glucose tolerance (IGT) [2]. It has been established that annually 5–10% of patients with IGT develop DM, over a five-year period – in 20–34%, and with a combination of impaired fasting glycemia (more than 5.5 mmol/l) and IGT – in 38–65% [3] .

The prevalence of LN among adult patients with DM is 0.1–3%. With diabetes in children, pathology occurs in 0.3%. According to the observations of researchers, there are significant fluctuations in different regions, especially among adolescents [4]. According to the state register of patients with DM in Moscow, LN is diagnosed in 0.5% of patients.

More often, LN occurs in type 1 diabetes (DM1) [5]. Clinical observations Marchetti et al. demonstrated an association between LN and MODY diabetes. Summarizing the cases described in the literature, the authors came to the conclusion that more often LN occurs in patients with DM1 (6.5%) and MODY-diabetes (2.8%), compared with DM2 (0.4%) [6] .

In studies with standard biochemical tests, DM in LN is diagnosed in 30–80% of patients. The study of the level of immunoreactive insulin, glucagon, cortisol and somatotropic hormone in the blood showed that disturbances in the hormonal regulation of carbohydrate metabolism are found in all patients with LN, including patients without signs of DM according to the results of determining fasting glycemia [7]. In this regard, in patients with LN without obvious signs of DM, it is necessary to conduct an oral glucose tolerance test in order to timely detect carbohydrate metabolism disorders.

There is evidence that women get sick three times more often than men [8]. The first symptoms of dermatosis usually occur between the ages of 20 and 60, although it can develop in both children and older people [5].

The literature describes examples of familial cases of LN [9].

LN as an independent disease without DM occurs in 10-50% of cases. Cases of LN association with autoimmune thyroid diseases, Crohn’s disease and ulcerative colitis, sarcoidosis, vitiligo [5, 10, 11] have been described, which can be explained by phenotypic and functional defects in cellular immunity. It is suggested that if a skin biopsy reveals FN with signs of active vasculopathy, especially with atypical localization of foci, further diagnostic search is necessary in order to identify a systemic disease (rheumatological, endocrine, hematological, etc.) underlying the pathological process [12].

Etiology and pathogenesis of LN. Pending issues

The etiology and pathogenesis of LN have not been fully studied, however, its occurrence and progression are characterized by multifactorial genesis against the background of immunological changes, disorders of carbohydrate and lipid metabolism, as well as pathology of microcirculatory processes [13].

An important role in the development of skin lesions is played by a violation of nervous trophism, dehydration of the skin against the background of autonomic neuropathy. The results of histochemical studies demonstrate the absence of intradermal nerves in the central part of the necrobiotic site and reveal only individual nerve fibers along the periphery, which may explain the decrease in sensitivity found in many patients [14].

Due to the fact that LN is closely associated with DM, in most studies, carbohydrate metabolism disorders are considered as the leading cause of the pathology. At the same time, metabolic changes can initiate deviations in lipid metabolism. In LN, significant quantitative changes in the lipid spectrum were revealed, expressed in an increase in the levels of triglycerides, total cholesterol, low and very low density lipoproteins, and a decrease in high density lipoproteins [15].

According to some researchers, diabetic microangiopathy is the leading pathogenic factor in skin lesions in LN. The cause of vascular pathology may be the activation of free radical processes in the lipids of cell membranes, which is aggravated by increasing hypoxia [16].

Clinical picture

Typical foci of necrobiosis are localized on the legs, while the lesion is often bilateral and symmetrical. In some cases, dermatosis is localized on the ulnar surface of the forearm, trunk, feet, face, scalp. The pathological process during the progression of the disease can spread to other areas of the skin and become disseminated in some patients [5].

The main elements in LN are represented by plaques, spots, nodules, ulcers. The boundaries are clear. Color varies from yellowish red to brown. Slight peeling may be observed on the surface, and a slight infiltration is determined at the base during palpation. Spotted, nodular elements as a result of peripheral growth gradually merge, forming plaques. The formed clinical picture of the classic form of LN is characterized more often by single elements, oval or polycyclic outlines, 2–10 cm in diameter, sharply demarcated from apparently healthy skin and rising above its level. The peripheral zone of the plaques is a ridge formed by hemispherical nodules, and the central part is somewhat sunken. Over time, the skin in the central zone of plaques becomes atrophic, and telangiectasias are visible on its surface [17].

Approximately 1/4 of patients with LN foci undergo ulceration, which is most often preceded by traumatic injuries. Ulcers are superficial, contain scanty serous or serous-hemorrhagic discharge, have scalloped edges and polycyclic outlines. After epithelialization of ulcers, the skin acquires a bumpy appearance with signs of cicatricial atrophy. Rash elements usually do not cause subjective sensations, but in the presence of a wound process, patients notice pain in the lesions [18].

A peculiar pattern of localization, number and size of lesions depending on the presence of concomitant DM was revealed. So, with moderate and severe DM, large single lesions are more often observed, which, as a rule, are localized on the shins, feet, less often on the thighs. In persons without diabetes, the rashes are small, multiple, located not only on the lower extremities, but also on the trunk, upper extremities, and face [19].

Diagnosis, research methods for LN

The diagnosis of LN is based on the results of clinical, biochemical and histological examination of the patient.

Histologically, with light microscopy, LN is characterized by limited foci of connective tissue necrobiosis, granulomatous inflammation of the lower layers of the dermis. In the element of lipoid necrobiosis, the epidermis is thinned, with smoothed interpapillary outgrowths. At all levels of the reticular dermis and in the septa of the subcutaneous adipose tissue, there are foci of necrobiosis of collagen fibers. Around the foci, a cellular infiltrate is observed, consisting of histiocytes, fibroblasts, epithelial and giant multinucleated cells. When stained with Sudan III, extracellular grains of phospholipids and cholesterol are detected in areas of necrobiosis. Around the vessels of the superficial and deep plexus, lymphohistiocytic infiltration with an admixture of plasma cells is observed. In blood vessels endothelial proliferation and infiltration is determined. Noticeable deposition of polysaccharides in the walls of blood vessels (positive PAS reaction). The lumen of vessels, especially small ones, is sharply narrowed up to obliteration, there are blood clots in the lumen. In the “granulomatous” part, necrobiotic masses have a small amount of vascular changes, and epithelioid and giant cells include most of the typical granulomatous changes. In old elements, the epidermis is thinned, thickened bundles of collagen are densely located, especially in the lower parts of the dermis and septa of the subcutaneous adipose tissue. Weakly expressed lymphohistiocytic perivascular and intraseptal infiltrates. Infiltration by histiocytes of the lower parts of the dermis is not sharply expressed [17, 4].

The subject of a separate study is the degeneration of collagen and elastin. Electron microscopy reveals loss of striation, disordered arrangement of collagen bundles, and pronounced differences in the diameter of individual collagen fibers. Collagen concentration, as measured by hydroxyproline, was significantly reduced in damaged skin areas. At the same time, the ratio of collagen types I and III was not changed. Fibroblasts derived from FN sites synthesized less collagen than apparently healthy skin cells. Reduced collagen synthesis was attributed to a decrease in the amount of messenger RNA for procollagen type I, measured by hybridization with a specific human cDNA clone (a DNA molecule synthesized according to the base sequences in mRNA using RNA-dependent DNA polymerase). Collagenase production by these cells was not increased. In areas with a disturbed structure of elastic fibers, overexpression of mRNA of macrophage metalloelastase, cells with the protein of macrophage metalloelastase, giving positive staining for the presence of urokinase-type plasminogen activator, was found [20].

Due to the close association between LN and DM, the function of the glucose transporter in damaged tissue was studied. Glut-1 serves to ensure the transport of glucose across the epithelial and endothelial barriers. Disorders of glucose transport by Glut-1 were first detected in fibroblasts in T2DM. The study examined Glut-1 expression in areas of collagen destruction in LN and in patients without diabetes with scars or granuloma annulare. For this, polyclonal antibodies to Glut-1 were used in a standard immunoperoxidase reaction. Glut-1 expression in areas of collagen degeneration has been shown to contribute to tissue insulin resistance [21].

Since vascular disorders are observed in LN, transcutaneous measurement of oxygen and carbon dioxide tension by an electrochemical method is used to assess tissue perfusion. Statistically significant hypoxia is detected in the atrophic center of the LN. At the border of the affected area, these violations are even more pronounced. Inhalation of pure oxygen significantly increases PcO2 in damaged areas, but these values ​​are much lower than in healthy areas of the skin. At the periphery of the damaged area, PcCO2 is much higher. These studies confirm the vascular origin of LN, including reduced perfusion in combination with impaired gas diffusion [16].

Ultrasound of FL foci showed that differentiation of skin layers was preserved, but the boundary between them was fuzzy and blurred, which may be due to granulomatous inflammation of the dermis [22]. Decreased echogenicity of the dermis in the foci of LN seems to be associated with connective tissue necrobiosis, degeneration and destruction of dermal fibers. The thickness of the skin layers varies statistically unreliably. EDC (Power Doppler Imaging) and CDC (Color Doppler Imaging) showed no excessive vascularity in the lesions [23]. The study of blood perfusion parameters in the lesions on the analyzer of capillary blood flow reveals an increase in the level of basal blood flow by an average of 50%, and the amplitude of vasomotion – by 40% compared with apparently healthy skin. In addition, a decrease in the reactivity of microvessels is recorded in the area of ​​rashes [24].

Of considerable interest is the determination of the expression of toll receptors in LN. The study of this issue will allow us to understand the mechanism of the disease and develop scientifically based approaches to its treatment. Toll-like receptors (TLRs) are the most important members of the family of pattern recognition receptors used by the innate immune system. Activation of TLR leads to the rapid involvement and activation of cells of the innate immune system: macrophages, dendritic cells, mast cells, monocytes, neutrophils, and the induction of proinflammatory and anti-inflammatory proteins, acute phase proteins, and costimulatory molecules. TLRs are involved in the development of a secondary specific immune response by inducing the formation of immunological memory. In addition, TLRs play an important role in the regulation of hematopoiesis, affect the differentiation of myeloid stem cells, the proliferation and differentiation of B- and T-lymphocytes, and can act as activators of apoptosis [25]. Currently, 10 types of human TLRs have been identified that are able to recognize lipids, proteins, nucleic acids, both coming from outside (fragments of microorganisms) and formed in the body (fibronectin, hyaluronic acid, heat shock protein).

TLRs are expressed on various cells. In the skin, TLRs are expressed by various cells, from the epidermis to the subcutaneous fat. Expression and function of TLRs are highly variable and dependent on cell type. The main cells expressing TLRs are keranocytes (expressing TLRs 1-6, 9) and Langerhans cells, which express all types of TLRs, especially 1, 2, 3, 5, 6, and 10. Monocytes/macrophages, T- and B-lymphocytes, endothelial cells, mast cells, fibroblasts, and adipocytes [26].

TLR activation plays a role in inflammation. The production of cytokines and chemokines triggers a cascade of reactions and activates antimicrobial defenses. Although this mechanism is useful in fighting infection, it can damage one’s own tissues and contribute to the development of septic shock. Mutations and TLR deficiency are the cause of increased susceptibility of the body and chronic infection and inflammation [26, 27]. Recently, information has appeared in the literature about the involvement of TLR in the development of pathological conditions not associated with infection. Thus, variations in TLR expression were demonstrated in atopic dermatitis, psoriasis, and ultraviolet irradiation [26, 27, 28].

Differential diagnosis

Clinical polymorphism of LN, the possibility of transition from one form to another, and its combination with other dermatoses can pose difficult diagnostic questions for the doctor.

Early manifestations of LN are difficult to differentiate from granuloma annulare, since pathological changes in the dermis may have similar features. However, as the lesion enlarges, a plaque area of ​​atrophy with yellow staining becomes clearly visible [17]. Granuloma annulare is characterized by the deposition of glycosaminoglycans in the foci of collagen dystrophy, which, when stained with toluidine blue, give metachromatic staining. With granuloma annulare, there is no ulceration of the epidermis, there are no vascular changes, giant cells and lipid deposits are not detected. It should be noted the great clinical similarity between scleroderma-like LN and plaque scleroderma at certain stages of the development of the process. In scleroderma, collagen bundles do not break, and no foci of necrobiosis are observed. When stained with Sudan III or IV, lipoid grains or their clusters are not detected [1]. The differential diagnosis should be made with rheumatoid nodules and necrobiotic xanthoma. The rheumatoid nodule is characterized by massive deposits of fibrin surrounded by a thin rim of palisade histiocytes. Necrobiotic xanthogranuloma, unlike LN, is more often localized paraorbitally and is associated with paraproteinemia [29], characterized by the presence of a large number of epithelioid cells and histiocytes with a “foamy” cytoplasm, located palisade around the zone of collagen fiber degeneration, the presence of a large number of extracellular lipids, massive necrosis of inflammatory infiltrate cells and adipocytes.

Conclusion

Thus, according to the literature data, LN is an urgent problem in medicine. It is observed in 0.1-3% of patients with DM and leads to the development of significant cosmetic defects.

Recently, new laboratory and instrumental methods have appeared (transcutaneous oximetry, duplex skin examination, immunological tests, modern microscopy techniques) that can be used in the diagnosis of LN. At the same time, the question of the pathogenesis of the disease remains open; there are no unified algorithms for diagnosis and treatment. Solving these problems requires further research using a multidisciplinary approach.

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Treatment of NECROBIOUS LIPID – Recommendations of the British Association of Dermatologists (translation and adaptation by Prof. Svyatenko)

What is the purpose of this article?

This article has been written to help you understand more about necrobiosis lipoidis . She will tell you what it is, what causes it, what can be done about it and where you can learn more about it.

What is necrobiosis lipoidis?

Necrobiosis lipoidis is an uncommon inflammatory condition in which shiny, reddish-brown, or yellowish patches develop on the skin, usually in young adults or early middle age. This condition most often occurs in combination with diabetes, both insulin-dependent and non-insulin dependent.

What causes necrobiosis lipoidis?

This is not entirely clear. Necrobiosis lipoidis is caused by damage to the fibers that give the skin strength (collagen fibers). Some believe it is due to changes in the small blood vessels in the skin.

Only one in three hundred diabetics have necrobiosis lipoidosis , but most patients with necrobiosis lipoid have or develop diabetes. Lipoid necrobiosis does not appear to be associated with diabetic control.

Necrobiosis lipoidis affects all races. It strikes at any age and is three times more common in women than men.

Necrobiosis lipoidis is not contagious or cancerous, but there is a small risk of developing skin cancer (squamous cell carcinoma) that develops with long-term lesions.

Is necrobiosis lipoidis hereditary?

No.

What are the symptoms of necrobiosis lipoidis?

Usually nothing but a rather unsightly appearance of discolored areas. However, the skin in areas of lipoid necrobiosis is often eroded, painful ulcers are not uncommon, especially after minor blows. It may take a long time for the ulcers to heal.

What does necrobiosis lipoidis look like?

Areas of necrobiosis lipoidis usually begin as one or more small, red, slightly raised areas on one or both legs.

Much less frequently, similar areas may develop elsewhere on the legs and even on the arms, trunk or face. These lesions grow slowly and may coalesce to form larger, flatter, irregular areas, usually with a well-defined red border and a shiny yellowish center with visible blood vessels. These spots usually persist.

Because the skin in these areas is thinned, it is prone to breaking down (splitting) into ulcers (with the layer of dead skin cells separated from the surrounding living tissue) with little damage to the skin. Ulcerated areas may be fragile (contain dead skin cells) and infected.

How can it be diagnosed?

Often the onset of symptoms is enough to make a diagnosis. If there is any doubt, your doctor may suggest a biopsy (a small sample of skin from one of the areas is removed under local anesthesia and examined under a microscope in a laboratory). For those diagnosed with necrobiosis lipoidis, tests for diabetes may also be suggested by the doctor.

How can necrobiosis lipoidis be treated?

Treatment works best in the early stages lipoid necrobiosis before scarring, but results are unpredictable and sometimes disappointing. It is possible not to treat necrobiosis lipoidis if there are no symptoms or ulceration. Rarely, the condition can go away on its own (up to 17%). Even when necrobiosis lipoidis resolves, it usually leaves permanent pigment spots and thinning of the skin.

The following treatments have helped some patients:

• The most common treatments are strong steroid creams or ointments or calcineurin inhibitors (tacrolimus ointment 0. 03% or 0.1%). These creams or ointments are sometimes covered with a plastic film and can help stop spreading patches.
• Steroid injections into inflamed areas necrobiosis lipoidis may be helpful, but there is a risk of skin thinning.
• A number of oral therapies have been tested in necrobiosis lipoidis with mixed results. These include pentoxifylline, nicotinamide, fumaric acid esters, thalidomide, antimalarial drugs, aspirin, and various immune-suppressing pills or injections.
• PUVA treatment (combination of long wavelength ultraviolet light and photosensitive tablet) may be helpful for some people.
• Photodynamic therapy (combination of red light and mild sensitizing cream) is only useful in some cases.
• Laser therapy (pulsed dye laser) may help reduce skin redness, but the benefits of using it are inconclusive. There is also a risk of skin ulceration after treatment and this is generally not recommended.
• Ulcerative necrobiosis lipoidis can be difficult to treat: simple pain pills and topical antiseptics, PUVA therapy, and immune-suppressing pills may be helpful.
• Surgical removal of lesions followed by skin grafting results in an unsatisfactory cosmetic result and the problem may recur.

Self care

• Protect necrobiosis lipoid lesions from injury to reduce the risk of ulceration. Consider protecting them with a soft bandage, elastic support stockings, or protective covers.
• If the stains are unsightly, you can cover them with cosmetics. It is worth getting professional help to find the best way to hide the area and apply makeup; Your doctor may suggest that you go somewhere that gathers to support people with conditions that affect their appearance.
• If you have diabetes, it’s best to try and keep it under control. There is little evidence that this will help Necrobiosis itself, but it may limit the risk of infections that can occur if the spots become ulcerated.
• If a lacerated, persistent blister or ulcer develops in the area of ​​ necrobiosis lipoidis , consult a physician without delay: early skin cancer can be easily treated.