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Introduction
Lupus erythematosus profundus (LEP) is a distinctive cutaneous marker of lupus erythematosus (LE) which.
While LEP was, in an earlier era, held to represent a manifestation of discoid LE (DLE) confined to the
skin, recent studies have shown LEP to occur with roughly equal frequency in the setting of systemic LE.
Clinical Features
LEP characteristically manifests as tan to violaceous plaques primarily affecting the head and neck area,
upper arms, and thighs, mainly afflicting women in the 3rd to 5th fifth decades. LEP may also be seen in
infancy. Lesions are characteristically symmetrical in disposition, may ulcerate, and generally heal with
atrophy. LEP may herald the onset of LE or occur in isolation. In most instances it occurs simultaneously
with other concurrent cutaneous and extracutaneous manifestions and occurs in roughly equal frequency in the
settings of discoid LE and systemic LE. We believe that LEP represents an unrepressed proliferation of
lymphocytes associated with ischemic injury to the panniculus, the latter reflecting humorally-mediated
enothelial cell injury. LEP may prove to be a form of CTD-related lymphoproliferative disease that follows
an indolent course.
Histopathology
The stereotypic histopathology of LEP comprises lobular infiltration of the panniculus by a dense
polymorphous and pleomorphic population of lymphocytes, histcocytes, and plasma cells with interposed zone
of granular necrobiotic alteration of the fat. Nodules of lymphocytes and plasma cells may recapituate
lymphoid follicles.
The histiocytic populace includes those whose cytoplasms contained abundant nuclear debris and others with
serpentine nuclear contours; these do not aggregate to form areas of granulomatous inflammation. The
lymphocyte populace is dominated by small and intermedate size forms with few immunoblasts and only rare
Sezary cells. Endothelial cell necrosis, segmental deposits of fibrin, occlusive luminal thrombi of
interstitial capillaries and venules obliterated by lymphocytes suggest that a microangiopathy is integral.
The appellation "lymphomatoid" is used in light of the inherent atypia of the infiltrating lymphocytes and
the dense obliterative nature of the angiocentric process, producing a constellation ofpicture reminiscent
of that seen in angioimmunoproliferative lesions. The characteristic epidermal changes of LEP in our hands
are restricted to a cell-poor interface dermatitis. Neurotropic, eccinotropic and angiotropic dermal
lymphoid inifltrates are seen in LEP, but are also seen in post-Herpetic eruptions, lymphoma, treponemal
infections, and morphea.
Direct immunofluorescence
A positive LBT is the rule in LEP when lesion are seen in the setting of SLE. In DLE, in contrast the LBT
is only positive if lesional tissue is sampled and corresponds to light microscopic epidermal alterations
characteristic of DLE.
Differential diagnosis
Relapsing polychondritis, Sjogren's syndrome, and dermatomyositis are other CTD's in which a lymphocytic
lobular panniculitis may be seen. LEP shares clinical features and histomorphology with subcutaneous T-cell
lymphoma (SCTCL), having a predilection for young women with a similar localization, namely, the extremities
or trunk, and in which CTD-like symptoms such as fever, anorexia, and leukopenia are frequent.
Pathologically, SCTCL shares with LEP infiltration of the fat lobule by a pleomorphic and polymorphous
lymphoid populace, karyorhexis, phagocytosis of debris by histiocytes, fat necrosis and a lymphoid vascular
reaction. Erythrocyte phagocytosis by histiocytes is not seen in LEP, while it is striking in SCTCL.
Patients with SCTCL have an almost universally poor prognosis, succumbing to hemophagocytic syndrome,
bacterial or fungal sepsis. Clonality, florid erythrophagocytosis, a dominance of CD8+ve lymphocytes and
loss of pan-T cell antigens such as CD5 are thus the main differentiating points to distinguish SCTCL from
LEP. There appears to be a subset of patients who manifest a waxing and waning course but lack the
fully-evolved criteria for diagnosis of SCTCL, a subgroup we term indeterminate lymphocytic lobular
panniculitis. This condition may represent a forme fruste of SCTCL.
References
- Burton JL, Cunliffe WJ. Lupus panniculitis. In : Champion RH, Burton JL, Ebling FJG, Ed's.Textbook of
Dermatology, 5th Ed'n. Oxford : Blackwell Scientific Publications, 1992:2144-6.
- Magro CM, Tawfik N, Crowson AN. Lymphomatoid granulomatosis. Int J Dermatol 1994;33:157-160
- Magro CM, Crowson AN, Harrist T. Atypical lymphoid infiltrates in cutaneous lesions of connective tissue
disease. Am J Dermatopathol 1997;19:446-455.
- Magro CM, Burns F, Kovatich A, Crowson AN. Lymphocytic lobular panniculitis : a clinical, histological,
immunophenotypic and genotypic study of 40 cases. J Cutan Pathol 2001;28:235-245
- Reed RJ, Clark WH, Mihm MC Jr. Disorders of the panniculus adiposus. Hum Pathol 1973;4:219-30
- Watanabe T, Tsuchida T. Lupus erythematosus profundus : a cutaneous marker for a distinct clinical subset-
Br J Dermatol 1996;134:123-125
- Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of systemic lupus erythematosus. Br J Dermatol
1996;135:355-362
PANCREATIC PANNICULITIS
Introduction/Clinical Features/Pathogenesis
Pancreatic panniculitis manifests clinically as painful or asymptomatic nodules or indurated plaques of
thighs, buttocks, lower trunk and distal lower extremities, associated with either acute pancreatitis or
pancreatic carcinoma, either symptomatic or asymptomatic. When associated with pancreatic carcinoma,
neoplasms are often of acinic cell type, although panniculitis has been reported in the setting of an islet
cell carcinoma. The etiopathogenesis is held to reflect the local action of blood-born pancreatic enzymes
including lipase and trypsin; cases of an identical panniculitis associated with circulating lipase or
amylase in the absence of pancreatic disease have been reported and support this construction. Some
patients with this condition also have polyserositis, arthritis or eosinophilia of peripheral blood.
Histopathology
The hallmark of pancreatic panniculitis is a form of enzymatic fat necrosis which maintains a ghost-like
architecture of the necrotic fat cells with liquefaction of cytoplasms but maintenance of the cytoplasmic
membranes. At the peripheral margins of the necrotic zones, one may see a variable neutrophilic infiltrate,
nuclear dust, deposition of basophilic calcium deposits (saponification) and hemorrhage. Some cases also
show the necrotic fat cells to have a pale basophilic hue due to the deposition of calcium salts. Older
lesions may show the added presence of giant cells, foamy histiocytes, hemosiderin and extension of the
inflammatory process into interlobular septae and dermis. With respect to differential diagnosis, we
believe that the histomoprhology of this form of panniculitis is practically pathognomonic; calciphylaxis
may mimic pancreatic panniculitis by showing calcium deposition in adipocytes but is distinguished by by
virtue of intimal and medial deposition of calcium.
MISCELLANEOUS FORMS OF PANNICULITIS
Painful nodular and plantar erythema of children:
A distinctive form of panniculitis has been described in children characterized by painful plantar erythema
and nodules at times accompanied by constitutional symptoms. Less than 30 cases have been reported. A
definite etiology with an infectious stimulus or an underlying autoimmune disorder has not been documented.
The lesions follow a course of spontaneous resolution. The term "painful nodular and plantar erythema of
children" has been applied. The histomorphology is reported to be one of septal and lobular panniculitis
with variable vasculitis.
Halogen associated necrotizing panniculitis:
Recently a form of necrotizing panniculitis ascoated with potassium bromide therapy has been described, and
to which the term halogen panniculitis has been applied. Potassium bromide is well known to be effective in
infants with severe myoclonic epilepsy. Halogen-associated necrotizing panniculitis forms part of a
systemic disease with crops of subcutaneous nodules, fever, elevated sedimentation rate,
hepatosplenomegalia, and abdominal pain. Histomorpholgically the picture is one of inflammation of adipose
tissues with infiltrating lymphocytes. Bromides may act as a chemokine and stimulate subcutaneous
inflammation.
Lipomembranous fat necrosis:
Lipomembranous fat necrosis is a distinct form of necrosis within the fat lobule characterized by micro and
macrocysts lined by amorphous eosinophilic material assuming a fern-like or crenulated appearance, devoid of
adipocyte nuclei. The linings and microgranules stain positively with periodic acid-Schiff, are resistant
to diastase, and also stain with Sudan black B. This form of necrosis is felt to be an ischemic sequel, with
the most common association being chronic venous insufficiency in middle aged obese women. The term
stasis-associated lipomembranous fat necrosis has been applied. However similar changes have been observed
in various deep dermal and subcutaneous disorders associated with vasculopathic reaction patterns such as
morphea, necrobiosis lipoidica, lupus panniculitis, calciphylaxis, CMV infection, post Herpes infection,
tetanus toxoid injection sites, and protein C deficiency.
Some authors use the term lipomembranous dystrophy to describe this distinctive form of fat necrosis.
References
- Arsura EL, Kilgore WB, Ratnayake SN. Erythema nodosum in pregnant patients with coccidioidomycosis. Clin
Infect Dis 1998;27:1201-3
- Cribier B, Caille A, Heid E, Grosshans E Erythema nodosum and associated diseases. A study of 129 cases.
Int J Dermatol 1998;37:667-72
- Diener W, Sorni M, Ruile S et l. Panniculitis due to potassium bromide. Brain Dev 1998;20:83-7
- Ramdial PK, Chetty R. Vaculitis-induced membranous fat necrosis. J Cutan Pathol 1999;26:405-10
- Sandraps E, Blomme S, Demeester A, Decroix J, Marot L, Lachapelle JM. Painful nodular and plantar erythema
in children. Ann Dermatol Venereol 1996;123:647-50
- Snow JL, Su WP Lipomembranous (membranocystic) fat necrosis. Clinicopathologic correlation of 38 cases. Am
J Dermatopathol 1996;18:151-5
- Tuerlinckx D, Bodart E, Despontin K, Boutsen Y, Godding V, Ninane J Sweet's syndrome with arthritis in an
8-month-old boy. J Rheumatol 1999;26:440-2
- Wilsher ML. Seasonal clustering of sarcoidosis presenting with erythema nodosum. Eur Respir J
1998;12:1197-9
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