Necrobiosis lipoidica L92.1

Rare, gynaecotropic, granulomatous systemic disease of unknown cause, which manifests itself on the integument and here preferably on the lower legs in the form of large, brown-red plaques which, if persisting for a long time, may also be ulcerated and then painful. An association with diabetes mellitus is present in about 65% of patients.

Granulomatosis disciformis chronica et progressiva is seen by some authors as a special form, by others as a differential diagnosis.

Common in diabetes mellitus patients. Frequency in diabetics: 3:1,000 patients.

In larger collectives, the following comorbidities are listed, although pathogenetic relationships (except for diabetes mellitus) cannot be postulated:

1. Diabetes mellitus type I (E10) 20.6%.
2. Diabetes mellitus type II (E11) 13.7%
3. Essential hypertension (I10) 9.2%
4. Ulcus cruris (L97): 7,3%
5. Other venous diseases, varices of the lower extremities (I87/3): 5.7%
6. Obesity (E66): 4,6%
7. Heart failure (I50): 4,1%
8. Lipoprotein metabolism disorders (E78): 2,3%
9. Psoriasis (L40): 2,3%
10. Erysipelas (A46): 2,3%
11. Multiple sclerosis (G35): 1.9%

Systemic granulomatosis of unknown etiology.

Associations with diabetes mellitus, hypertension, Crohn's disease, ulcerative colitis, granuloma anulare, or cutaneous sarcoidosis have been described (see previously).

Vascular changes ( microangiopathy, fibronectin and factor 8 associated antigen elevation, disturbances in prostaglandin synthesis), changes in sweat glands, collagen disturbances, immune mechanisms, disturbed leukocyte functions are discussed. Occasional occurrence in older scars has been reported (see Fig.).

The extent to which trauma (in the case of a senescent disposition) plays an initiating role remains open. However, localizations at mechanically exposed sites support this hypothesis.

Mainly occurring in middle age (50-55 years). Approximately 10% of those affected are in the age groups 75-80 and 15-20 years. Women are affected 2-3 times more frequently than men (recent figures show a ratio of 6:4).

Frequently occurring after a (often not remembered) minor trauma, irregularly configured, sharply demarcated, atrophic, indurated plaque with a yellow to brownish-yellow, speckly shiny center, interspersed with telangiectasias. The initial focus is barely the size of a coin, clinically unremarkable, and often misrecognized as a traumatic hemosiderin deposit. Early lesional hair loss is suggestive of necrobsiosis lipoidica.

However, a reddish-purple to brown-red rim indicates ongoing inflammatory activity and peripheral growth.

The focus(s) show gradual centrifugal growth over months and years. The subcutis may also be involved in granulomatous inflammation. This deep component results in atrophy of the subcutaneous adipose tissue with depression of the atrophic surface. This results in increased vulnerability of the foci. Confluence of multiple foci is possible, resulting in map-like plaques (see Fig.).

In about 30% of cases, poorly healing, painful ulcers with a yellowish speckled, necrotic base develop in the lesions, following trivial trauma; depending on the localization (e.g., tibial edge), (painful) concomitant periostitis may also occur.

Healing with atrophy of skin and subcutaneous fat with (early) loss of skin appendages is possible.

Special forms: Necrobiosis lipoidica maculosa disseminata, necrobiosis lipoidica on forehead and head area. In the area of the hairy head (extremely rare localization) formation of a pseudopelade.

Epidermis thinned, otherwise without specific changes. In the middle and lower dermis, sometimes also in the subcutaneous adipose tissue, there are nodular or striated granulomatous inflammatory zones consisting of histiocytes, epithelioid cells and multinucleated giant cells of varying composition, as well as focal nests of lymphocytes and plasma cells.

Sporadic formation of lymphoid follicles. In some cases plasma cells may dominate the picture.

In addition to this inflammatory component, the cutis is characterized by extensive degenerative changes of the collagen (collagen necrobiosis). The zones of necrobiosis may occur in the midst of a granulomatous nodule, but may also alternate with granuloma zones in a sandwich-like fashion.

Wall-thickened or occluded vessels may be consistently detectable. Granulomatous inflammation may involve the subcutaneous fat tissue.

The extent to which granulomatosis disciformis chronica et progressiva represents an independent entity remains to be discussed.

Granuloma anulare

Sarcoidosis

circumstrictive scleroderma

ulcerated tubero-serpiginous syphilid (very rare)

chronic venous insufficiency

atypical mycobacteriosis

A plethora of different therapeutic proposals exist, which on the other hand means that there is no such thing as "the promising form of therapy". The treatment has to be adapted to the local situation (age of the lesion, large or small foci, ulcerated or non-ulcerated) and to a possible underlying systemic disease (e.g. diabetes mellitus). Important: Any treatment approach requires patience from both physician and patient. It is to be applied for years.

Treatment of the underlying disease, e.g. diabetes mellitus (adjustment of blood sugar!), hypertension, Crohn's disease (see Enteritis regionalis), ulcerative colitis. As a rule, however, treatment of the underlying disease does not improve the cutaneous symptoms.

In the case of localization on the lower legs, therapy should always be accompanied by consistent compression therapy, since this relatively often prevents progression and promotes healing (always perform arterial Doppler sonography before compression therapy).

• Non-ulcerated skin lesions:
  • Therapy of choice are topical glucocorticoids, e.g. Mometasone (Ecural®) under occlusion. Permanent wearing, change once/day for 14 days up to 4 weeks.
  • In a case report healing of the NL was reported under a local therapy with 0,1% tacrolimus (Protopic®)
  • Alternative:
    • Injectglucocorticoids intrafocally, once a month for 2-3 months, e.g. triamcinolone acetonide (e.g. Volon A 10 1:1 with scandicain). Caution: Painfulness; Compliance!
    • Good results were reported from PUVA therapy.
• Ulcerated lesions:
  • Ulcer-adapted wound therapy. .

In case of ulceration or highly inflammatory component, try systemic therapy with glucocorticoids in medium dosage such as prednisolone 60-80 mg/day (e.g. Decortin H) for one week, then 30 mg/day for one month. Caveat. Monitor blood glucose levels! After ulcers have healed, transition to non-steroidal alternative therapy (e.g., fumaric acid esters or TNF-alpha blockers).

Alternative: Fumaric acid esters in the therapeutic modality indicated for psoriasis (see below Psoriasis vulgaris).

Alternative: Ciclosporin A systemically: Initial 2.5-7.5 mg/kg bw/day p.o., after one month gradual reduction to a maintenance dose of 1-2.5 mg/kg bw/day. By determining the blood plasma level, an optimal active level of 100-200 ng/ml can be set (blood collection in the morning, before taking the preparation!).

Alternative: Therapy trial with the TNF-alpha blocker Adalimumab (initially 80mg s.c.,1 week later 40mg s.c.; maintenance therapy 40mg s.c. every 14 days).

Alternative: Mycophenolate mofetil systemic: Initially 2.5-7.5 mg/kg bw/day p.o. As maintenance therapy mycophenolate mofetil monotherapy with 1.0 g/2 times/day p.o..

Alternatively or additively: Pentoxifylline (e.g. Trental) 3 times/day 400 mg p.o. or Nicotinamide (e.g. Nicobion 3 times/day 500 mg p.o. can be tried supportively. In persistent cases, if necessary, acetylsalicylic acid 1.5-4.5 g/day p.o., dipyridamole (Curantyl) 225 mg/day p.o. singly or in combination (Aggrenox)...,

Experimental: Assuming that tissue hypoxia is a major cause of the disease, experimental approaches attempt to achieve improvements by oxygenating the blood.

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4. Beattie PE et al (2006) UVA1 phototherapy for treatment of necrobiosis lipoidica. Clin Exp Dermatol 31: 235-238
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