Necrobiosis lipoidica and sarcoidosis

We report the case of a female patient with necrobiosis lipoidica of the lower legs and coexistent systemic and cutaneous sarcoidosis. We review the six previously reported patients with coexisting necrobiosis lipoidica and sarcoidosis. The associations between the granulomatous disorders of the skin, especially necrobiosis lipoidica, sarcoidosis and granuloma annulare, are discussed. The common pathogenetic features of these disorders are reviewed.     

Lymphokines (MIF) in the serum of patients with sarcoidosis and cutaneous granuloma annulare

Serum MIF activity was studied in ten patients with sarcoidosis, fourteen with granuloma annulare, four with necrobiosis lipoidica, and nine with various dermatological diseases. Positive MIF activity was found in the sera of nine of the ten patients with sarcoidosis and eleven of the fourteen patients with granuloma annulare. The delayed hypersensitivity tests were negative in all nine of the patients with sarcoidosis who had serum MIF activity and were positive in only three patients with cutaneous sarcoid lesions. One of four patients with necrobiosis lipoidica demonstrated minimal serum MIF activity. Data on serum lymphokine activity in sarcoidosis and granuloma annulare suggest that these two diseases are related to delayed hypersensitivity mechanisms.     

Cutaneous Sarcoidosis Clinically Mimicking Necrobiosis Lipoidica in a Patient with Systemic Sarcoidosis

A 70-year-old woman with an 8-year history of systemic sarcoidosis developed round, red-brown eruptions, with central atrophic lesions on her lower legs. The features of the biopsy specimen resembled those of necrobiosis lipoidica (NL), but although necrobiosis was present there were well-formed non-necrotizing granulomas in the dermis. The histological diagnosis was cutaneous sarcoidosis. Systemic sarcoidosis presenting with NL has rarely been reported. The histological features of cutaneous sarcoidosis sometimes mimic those of other granulomatous diseases, including NL and granuloma annulare, which are difficult to distinguish. We discuss the novel association between sarcoidosis and other granulomatous diseases.     

T-zone histiocytes in granulomatous skin diseases

We investigated the distribution of T-zone histiocytes by immunohistochemical demonstration of S-100 protein in granulomatous skin diseases (granuloma annulare, 8 cases; necrobiosis lipoidica, rheumatoid nodule, sarcoidosis, lupus vulgaris, and foreign-body granuloma; 5 cases each). T-zone histiocytes were regularly found in the lymphohistiocytic mantle, but also occasionally between epitheloid cells. Our results show that, besides the monocyte-macrophage system, T-zone histiocytes consistently contribute to the formation of cutaneous granulomas. These findings may indicate a role of delayed-type hypersensitivity.     

Annular elastolytic giant cell granuloma. A clinicopathologic study of five cases and a review of similar entities

Five patients with annular lesions of the face, scalp, and other exposed surfaces were studied using the radial triple zone biopsy technic. Interestingly, one of the patients had necrobiosis lipoidica diabeticorum (NLD) and another had systemic sarcoidosis. Clinically, the lesions were annular patches with erythematous borders and hypopigmented centers. The histopathology of the lesions showed many multinucleated giant cells, (often with prominent asteroid bodies), histiocytes, lymphocytes, scattered epithelioid cells, total lysis of elastic tissue, no necrobiosis, and absence of both mucin and lipid. This entity can be differentiated from granuloma annulare (GA), NLD, and cutaneous sarcoidosis. It is identical with several previously described entities; we propose a more appropriate term: "annular elastolytic giant cell granuloma (AEGCG)."     

Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare

Using an antibody to S100 protein, the number of dendritic cells above the basal layer in the epidermis was assessed in necrobiosis lipoidica and granuloma annulare. A statistically significantly higher number of these cells was found within the epidermis in necrobiosis lipoidica compared with granuloma annulare and normal skin. The numbers were similar to those seen in sarcoidosis and tuberculous reactions in the skin, which raises the possibility of an immune pathogenesis for necrobiosis lipoidica.     

Cutaneous sarcoidosis in southern Taiwan: clinicopathologic study of a series with high proportions of lesions confined to the face and angiolupoid variant

Background Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. Our clinical experience suggests that facial involvement and the angiolupoid variant appear more common in our patients compared with series reported from the western countries. Objective To characterize the clinicopathologic features of cutaneous sarcoidosis diagnosed in our department and to compare our data with those in the literature. Methods We conducted a clinicopathologic review of biopsy‐proved cases of cutaneous sarcoidosis diagnosed during January 2002–December 2010. Results Our study consisted of 37 patients, ages 26–84 years (mean 54.3 years), of whom 84% were females. Systemic involvement was detected in 73%, affecting the lung in 57%, lymph nodes in 65% and eyes in 43%. Most skin lesions were the papulonodular type (70%) and confined to the face (54%). The angiolupoid variant, while rare in Europe and America, was the most common variant (38%) in our series and often associated with eye involvement. The histology was characterized by infiltration of naked sarcoidal granulomas, mostly (86%) mixed with variable amounts of tuberculoid granulomas in the dermis and/or the subcutis. Other findings included fibrinoid necrosis (23%), foreign bodies (16%), osteoclast‐like cells (14%) and granuloma annulare‐like and necrobiosis lipoidica‐like features. Conclusion The present series of cutaneous sarcoidosis was characterized by a marked female predominance and by high proportions of facial involvement and the angiolupoid variant. Angiolupoid sarcoidosis was often associated with eye involvement. A complete dermatologic examination and biopsy of suspicious skin lesions should be routinely performed to facilitate early diagnosis of sarcoidosis.     

Links Between Granuloma Annulare,Necrobiosis Lipoidica Diabeticorum and Childhood Diabetes: A Matter of Time?

Abstract: Diabetes mellitus is associated with a range of dermatologic presentations, including granuloma annulare and necrobiosis lipoidica diabeticorum. Granuloma annulare occurs earlier than necrobiosis lipoidica diabeticorum and the association with diabetes mellitus is much weaker. We describe two children with diabetes who both developed granuloma annulare and later, necrobiosis lipoidica diabeticorum. We postulate that the early onset and transient nature of granuloma annulare, compared with the later onset and persistence of necrobiosis lipoidica diabeticorum, might account for the different apparent rates of association with diabetes mellitus.     

Eosinophils in the cellular infiltrate of granuloma annulare

Eosinophils have been described in the infiltrates of granuloma annulare, but their frequency, distribution and extent are not well documented. We found eosinophils in 18/45 (40%) cases of granuloma annulare, without significant variation relating to histologic sub-pattern. Eosinophils were seen in over half the cases of deep granuloma annulare and in over one-third of the cases of superficial granuloma annulare. This study demonstrates the lack of specificity of eosinophils in differentiating superficial granuloma annulare from deep granuloma annulare, granuloma annulare from necrobiosis lipoidica, and granuloma annulare from occasional clinical simulants which histologically show eosinophils, such as arthropod bite reactions.     

Necrobiosis lipoidica of the glans penis

We report a 65-year-old diabetic man with necrobiosis lipoidica occurring on the glans of penis. He was initially seen with chronic ulcerative balanitis that eventually healed with strict control of diabetes mellitus, cystostomy, and pentoxifylline, leaving heavily depressed scars. Penile necrobiotic palisading granulomas include necrobiosis lipoidica and granuloma annulare. On the basis of the literature review, these 2 diseases manifest different skin lesions.     

Simultaneous occurrence of ulcerated necrobiosis lipoidica and granuloma annulare in a patient: case report

Simultaneous occurrence of granuloma annulare and necrobiosis lipoidica is quite rare. There are seven reported cases in the literature, but only one presenting ulcerated necrobiosis lipoidica. We report a 39-year-old male with histopathologically confirmed granuloma annulare and ulcerated necrobiosis lipoidica, without diabetes mellitus.     

Interstitial granulomatous lesions as part of the spectrum of presenting cutaneous signs in pediatric sarcoidosis

Abstract:  Skin findings in childhood sarcoidosis vary greatly, but only a few occurrences have been published in which the histopathology has been characterized well. We describe a child with sarcoidosis in whom the cutaneous findings were atypical, resembling granuloma annulare. Histologic examination of these cutaneous lesions, however, revealed areas of sarcoid-like epithelioid cell granulomas, a palisading granulomatous process with features of granuloma annulare, as well as palisading neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis. This underscores the variability of skin findings in childhood sarcoidosis—even within the same patient—and suggests that sarcoidosis should be considered in the differential diagnosis of children initially diagnosed with granulomatous skin lesions, such as granuloma annulare, palisading neutrophilic, and granulomatous dermatitis or interstitial granulomatous dermatitis, who demonstrate associated signs of systemic disease.     

Necrobiosis Lipoidica-like Skin Lesions in Systemic Sarcoidosis

A 62-year-old woman with systemic sarcoidosis developed erythematous plaques on her lower legs. Clinically, two kinds of skin lesions were distinguished; one type formed brownish-red plaques with induration suggesting plaque-type skin sarcoid, and the other formed purplish erythematous plaques with atrophic centers resembling necrobiosis lipoidica. In spite of this clinical appearance, a biopsy specimen from one of the latter lesions revealed typical skin sarcoid histology composed of discrete non-caseating granulomas, while that from one of the other lesions showed necrobiotic changes of collagen bundles surrounded by epitheloid histiocytes and foreign-body giant cells. Because cutaneous involvement of sarcoidosis may mimic necrobiosis lipoidica clinically and/or histologically, we diagnosed her skin lesions as necrobiosis-like skin sarcoid.     

Increased plasma fibronectin in diabetes mellitus, necrobiosis lipoidica and widespread granuloma annulare

The plasma level of fibronectin was measured in patients with granuloma annulare, necrobiosis lipoidica and diabetes mellitus and compared with levels in healthy controls. A significant increase was observed in necrobiosis lipoidica, generalised granuloma annulare and diabetes but not in patients with solitary lesions of granuloma annulare. The possible role of fibronectin in the development of micro-angiopathy is discussed.     

Collagenolytic (necrobiotic) granulomas: part II--the 'red' granulomas

A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers. The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. 'blue' granulomas vs. 'red' granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In the previously published first part, the clinical presentation, pathogenesis and histologic features of the 'blue' collagenolytic granulomas were discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In this second half of the series, the 'red' collagenolytic granulomas are discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg-Strauss syndrome, and eosinophilic cellulitis (Well's Syndrome).     

Superficial ulcerating rheumatoid necrobiosis: a perforating rheumatoid nodule

We report a case of superficial ulcerating rheumatoid necrobiosis (SURN), which is a recently described cutaneous manifestation of severe rheumatoid arthritis. As with classic rheumatoid nodule, there is evidence that this lesion may result from a vasculitis. SURN appears to represent a form of "perforating" rheumatoid nodule, and completes a triad of major necrobiotic processes (granuloma annulare, necrobiosis lipoidica, rheumatoid nodule) that have been reported to show epidermal perforation.     

Localization of angiotensin converting enzyme (ACE) in granulomas of sarcoidosis cutaneous lesions

Using an immunofluorescent technique, the localization of angiotensin converting enzyme (ACE) was investigated in granuloma lesions from the skin of three sarcoidosis cases. Specific fluorescence was observed in epithelioid cells in the sarcoidosis granulomas examined. However, it was not found in any other granulomatous diseases observed as controls, which included granuloma annulare, foreign body granuloma and lupus miliaris disseminatus faciei. These results indicate that ACE is specifically localized in the epithelioid cells in cutaneous granuloma lesions of sarcoidosis; in one case, it was also observed in Langhans giant cells. Therefore, it is suggested that examination for ACE in cutaneous lesions using an immunofluorescent technique is very useful for the diagnosis of sarcoidosis in the skin. We suggest that epithelioid cells of granulomas in sarcoidosis cutaneous lesions may play an important role in the increase of serum ACE activity.