The Differential Diagnosis of EN

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Dear Newer Group Members,Often new members tell me they are sure they must have EN based on the appearance of the nodules. And just as often I will be notified that when they wen to a doctor it turns out to be something else. Here is an article which describes the various possibilities besides EN which look quite a bit like it: Erythema Nodosum from Dermatology Online Journal Differential DiagnosisErythema

induratum of Bazin is the main differential diagnosis for erythema

nodosum. The clinical picture or erythema nodosum differs from erythema

induratum of Bazin in showing lesions usually located on the shins that

regress in a few weeks with no tendency for necrosis and scarring. In

contrast, typical lesions of erythema induratum of Bazin appear on the

posterior aspects of the legs of adult women with erythrocyanotic

circulation, are more persistent, often ulcerate (Figure 16), and

regress leaving an atrophic scar. In atypical cases, the differential

diagnosis between these two entities may be solved by histopathological

examination, because erythema nodosum is a mostly septal panniculitis,

whereas erythema induratum of Bazin is a predominantly lobular

panniculitis (Figure 17).[157] For this differential

diagnosis, biopsy specimens taken by scalpel excision are preferable to

punch biopsies, and when available, early lesions from as proximal a

site as possible should be selected. Table 2 summarizes the main clinical and histopathological differences between erythema nodosum and erythema induratum of Bazin. Figure 16.

(click image to zoom) Erythema induratum of Bazin involving the

posterior aspect of the leg of an adult woman with erythrocyanotic

circulation and ulcerated lesions. Figure 17.

(click image to zoom) Histopathologic features of erythema induratum of

Bazin. A: Scanning power shows a mostly lobular panniculitis. B: Higher

magnification shows thickened septa, but the inflammatory infiltrate

involves mostly the fat lobules. C: Still higher magnification shows

the inflammatory infiltrate in the fat lobules and the involvement of a

blood vessel in the thickened septa. D: Still higher magnification

demonstrates that the inflammatory infiltrate involves the vessel wall

and obliterates the lumen. (A-D, Hematoxylin-eosin stain; original

magnifications: A, x20, B, x40, C, x200, D, x400).Cutaneous

lesions of superficial thrombophlebitis may show a clinical appearance

similar to that of erythema nodosum. However, the lesions are usually

located on the sides of the lower legs and consist of hard, irregular

and fibrotic cords or plaques rather than erythematous nodules (Figure

18). A biopsy of these lesions demonstrates that the affected vein

appears with luminal thrombosis and with inflammatory infiltrate within

its wall (Figure 19). In contrast to erythema nodosum, and despite the

intense damage of the involved vein with dense inflammatory infiltrate,

lesions of superficial thrombophlebitis show little or no inflammatory

infiltrate in the connective tissue of the septa and the adjacent fat

lobule, and the process is more vasculitic than panniculitic.[158] Figure 18.

(click image to zoom) Superficial thromboflebitis. Erythematous nodules

in liner arrangement with a cordlike thickening of the subcutis along

the involved vein. Figure 19.

(click image to zoom) Histopathologic features of superficial

thrombophlebitis. A: Scanning power shows thrombosis of a large blood

vessel within thickened septa. B: Higher magnification shows the

inflammatory infiltrate centered in a large blood vessel of the

thickened septa. C: Still higher magnification shows that the involved

vessel had several muscular fascicles in its wall. D: Still higher

magnification demonstrates the inflammatory infiltrate involving the

muscular layers of this vein and the obliteration of its lumen. (A-D,

Hematoxylin-eosin stain; original magnifications: A, x20, B, x40, C,

x200, D, x400).Cutaneous

polyarteritis nodosa can also present as bilateral tender erythematous

nodules on the lower legs. However, the involved area usually shows

livedo reticularis; the nodules are preferentially located on the

calves and often ulcerate (Figure 20). Histopathologically, lesions of

cutaneous polyarteritis nodosa show vasculitis involving medium sized

arteries and arterioles at the septa of the subcutaneous tissue. The

involved vessels appear with a thickened wall, and characteristically,

the tunica intima of the involved artery exhibits an eosinophilic ring

of fibrinoid necrosis, giving a targetlike appearance to the vessels

(Figure 21).[158] As in superficial thrombophlebitis,

cutaneous polyarteritis nodosa is a vasculitic process with little or

no inflammatory involvement of the adjacent septa and lobules of the

subcutaneous tissue. Figure 20.

(click image to zoom) Cutaneous polyarteritis nodosa presents with

tender erythematous nodules on the lower legs that often ulcerate The

involved area usually shows livedo reticularis. Figure 21.

(click image to zoom) Histopathologic features of cutaneous

polyarteritis nodosa. A: Scanning power shows sparse inflammatory

infiltrate in the subcutis. B: Higher magnification shows the

inflammatory infiltrate centered in a blood vessel. C: Still higher

magnification shows an eosinophilic ring of fibrinoid necrosis at the

tunica intima of the involved blood vessel. D: Still higher

magnification of the eosinophilic ring of fibrinoid necrosis giving a

targetlike appearance to the vessel. (A-D, Hematoxylin-eosin stain;

original magnifications: A, x20, B, x40, C, x200, D, x400).Because

fully developed lesions of erythema nodosum are histopathologically

characterized by a granulomatous component, subcutaneous sarcoidosis

(Figure 22) should also considered. However, in subcutaneous

sarcoidosis granulomatous involvement predominates in the fat lobules

rather than in the septa (Figure 23), and the septa do no exhibit the

fibrosis and the thickening usually seen in fully developed lesions of

erythema nodosum.[157] Figure 22. (click image to zoom) Subcutaneous sarcoidosis. Erythematous nodule on the forearm. This patient had also lung sarcoidosis. Figure 23.

(click image to zoom) Histopathologic features of subcutaneous

sarcoidosis. A: Low-power view shows the involvement of the fat

lobules. Note sparing of the dermis. B: Higher magnification

demonstrates the granulomatous nature of the inflammatory infiltrate.

C: Still higher magnification shows that each collection of

inflammatory cells consisted of small noncaseating granuloma. D: Still

higher magnification demonstrates the presence of multinucleated giant

cell in the noncaseating granuloma. (A-D, Hematoxylin-eosin stain;

original magnifications: A, x40, B, x80, C, x200, D, x400).Erythema

nodosum leprosum is an inadequate term to describe an immune-complex

vasculitic process involving the dermis of patients with lepromatous

leprosy. The term is misleading because it may easily be confused with

authentic erythema nodosum. In most cases the process develops when

therapy results in massive death of lepra bacilli and the lesions

present not only as nodules, but also as necrotic, pustular or

hemorrhagic lesions.[159] The face, which is rarely involved

in authentic erythema nodosum, is a frequent location for lesions of

erythema nodosum leprosum .[159] In doubtful cases a biopsy

should easily distinguish between the two. Erythema nodosum leprosum is

a process involving the dermis, and when it extends to the subcutaneous

fat, the small blood vessels of the fat lobule are severely damaged and

appear with fibrinoid necrosis of their wall and luminal thrombi.

Special stains demonstrate numerous dead and degenerated acid-fast

bacilli.[160] In contrast, biopsies of erythema nodosum show a mostly septal panniculitis without vasculitis.Plantar

erythema nodosum should be differentiated from the so-called traumatic

plantar urticaria, which consists of tender erythematous nodules which

develop on the soles of children after physical activity.[161]

Some authors believe that plantar erythema nodosum and traumatic

plantar urticaria in children are the same entity rather than two

different processes, although the lesions reported as traumatic plantar

urticaria regressed in a few hours or days. Furthermore,

histopathologic study demonstrated a perivascular inflammatory

infiltrate of neutrophils and lymphocytes in the papillary and

reticular dermis.[161] However, the biopsies of those cases

reported as traumatic plantar urticaria contained no subcutaneous fat

at all, and therefore a diagnosis of plantar erythema nodosum could be

not definitely ruled out.[161,162] Palmoplantar erythema

nodosum in children should be also differentiated from idiopathic

palmoplantar neutrophilic eccrine hidradenitis, which is also

clinically characterized by painful erythematous nodules involving the

palms and soles of children that appear after physical activity.[163,164,165,166,167,168,169,170]

However, the histopathologic differential diagnosis between idiopathic

palmoplantar neutrophilic hidradenitis and erythema nodosum is

straightforward, because in the former the neutrophilic infiltrate is

surrounding and within the eccrine coils of the deeper dermis, whereas

in early erythema nodosum, neutrophils of the inflammatory infiltrate

are interstitially arranged between collagen bundles of the septa of

the subcutaneous tissue.Cutaneous B-cell lymphoma may present

with erythematous tender nodules on the lower extremities mimicking

erythema nodosum clinically (Figure 24).[171,172] However

histopathologic study reveals atypical lymphocytes, with hyperchromatic

nuclei and mitotic figures involving both the septa and the fat lobule

(Figure 25) or within the lumina of the blood vessels of the

subcutaneous fat in cases of intravascular B-cell subcutaneous lymphoma.[171,172] Figure 24. (click image to zoom) Subcutaneous lymphoma mimicking erythema nodosum. Erythematous tender nodules on the lower extremities. Figure 25.

(click image to zoom) Histopathologic features of subcutaneous

"panniculitic" lymphoma. A: Scanning power shows the involvement of

both septa and fat lobules. B: Higher magnification shows the

infiltrate involving the fat lobules and the thickened septa. C: Still

higher magnification demonstrates that the cell infiltrate extends from

the septa into the periphery of the fat lobules between individual fat

cells in a lace-like fashion. D: Still higher magnification

demonstrates atypical lymphocytes with pleomorphic and hyperchromatic

nuclei. E: Still higher magnification shows better that these are not

inflammatory but neoplastic lymphocytes (A-E, Hematoxylin-eosin stain;

original magnifications: A, x20, B, x40, C,