Panniculitis

Abstract

The panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat. The clinical findings are often insufficient for establishing diagnosis, and a biopsy is usually necessary to establish the specific diagnosis. The panniculitides may be histopathologically classified into mostly septal or mostly lobular panniculitis according to the structures of the subcutaneous tissue where the inflammatory infiltrate is more abundant. The second step in the histopathologic diagnosis is to assess whether vasculitis is present or absent. If it is present, the size and the nature of the involved blood vessel must be determined. The third step will be to identify the nature of the cells present in the inflammatory infiltrate and, finally, to look for additional histopathologic features that allow a specific diagnosis of the disease involving the subcutaneous fat.

Keywords

Alpha-1 antitrypsin deficiency panniculitis, Erythema induratum, Erythema nodosum, Lipoatrophy, Lipodystrophy, Pancreatic panniculitis, Panniculitis, Superficial migratory thrombophlebitis

Key Points

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The panniculitides comprise a heterogeneous group of inflammatory diseases that involve the subcutaneous fat.
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Various panniculitides may show the same clinical appearance, consisting of erythematous nodules, which frequently makes histopathologic study necessary in order to obtain the specific diagnosis.
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In patients presenting with panniculitis, performing an excisional biopsy that incorporates at least a fat lobule and its surrounding connective tissue septa is crucial in making the correct diagnosis.
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From a histopathologic point of view, most panniculitides are somewhat mixed because the inflammatory infiltrate tends to involve both the septa and the lobules. However, differentiating between a predominantly septal and a predominantly lobular panniculitis is often straightforward at scanning magnification on the basis of identifying the subcutaneous structures more intensely involved by the inflammatory infiltrate.
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Erythema nodosum, a predominantly septal panniculitis, is the most common form of panniculitis.
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Erythema induratum and nodular vasculitis have generally been considered to be synonyms referring to a clinicopathologic entity with several possible causes, one of which is tuberculosis.

Introduction

Panniculitis refers to inflammation within the subcutis. As for most inflammatory skin disorders, it is especially true for panniculitis that a combined assessment of all available clinical, laboratory, and histopathologic features may be required in order to establish a correct diagnosis. From a clinical point of view, different types of panniculitis with diverse etiologies can closely resemble one another clinically. There is usually deep induration or inflammation of the skin, accompanied by erythema, warmth, pain, and occasionally ulceration or drainage. Sometimes, panniculitis may represent the dermatologic manifestation of a systemic disease, with erythema nodosum (EN) being a classic example. Moreover, histopathologic differences among the various forms of panniculitis may be very subtle, as the subcutaneous fat responds in a limited number of ways to different stimuli. Therefore, when performing a biopsy in a patient with panniculitis, it is crucial to include an entire fat lobule and its surrounding connective tissue septa. Excisional biopsies are preferable to punch biopsies. Furthermore, panniculitis, like other inflammatory diseases of the skin, constitutes a dynamic process in which both the composition and the distribution of the inflammatory infiltrate may change within the course of a few days, making the achievement of the correct diagnosis challenging. Finally, management of patients with panniculitis may also be difficult, particularly given that treatment of both the specific panniculitis and the underlying illness is often necessary.

Table 12-1 provides a pattern-based histologic classification of the multiple forms of panniculitis. The categories have been determined based on histopathologic features, as septal versus lobular panniculitis, according to the location in which the inflammatory infiltrate is more abundant. Although there is no purely septal or purely lobular panniculitis, certain forms of panniculitis can be characterized as having predominantly septal or lobular involvement, and this finding can provide a useful clue to diagnosis when combined with other histopathologic features, such as the presence or absence of vasculitis and the nature of the cells present in the inflammatory infiltrate. Not all of the disease entities in Table 12-1 are presented in detail in this chapter, and the reader is referred to other chapters of this publication or to the suggested reading material for a comprehensive review of this subject.

TABLE 12-1

Proposed Classification of Panniculitides

Predominantly septal	Without vasculitis	Erythema nodosum
		Subacute nodular migratory panniculitis
		Necrobiotic xanthogranuloma
		Rheumatoid nodule
		Subcutaneous granuloma annulare
		Morphea profunda
		Necrobiosis lipoidica
	With vasculitis	Superficial migratory thrombophlebitis
		Cutaneous polyarteritis nodosa
		Leukocytoclastic vasculitis
Predominantly lobular	Without vasculitis	Noninflammatory	Inflammatory
		Sclerosing panniculitis Calciphylaxis Oxalosis Sclerema neonatorum	Pancreatic panniculitis Alpha-1 antitrypsin deficiency Cold panniculitis Lupus panniculitis (and other connective tissue disease-associated panniculitis) Pancreatic panniculitis Infective panniculitis Factitial panniculitis Cytophagic histiocytic panniculitis Traumatic panniculitis	Lipoatrophy Fat necrosis of the newborn Gout panniculitis Crystal storing panniculitus Poststeroid panniculitis Postirradiation panniculitis Sclerosing panniculitis (lipodermatosclerosis)
	With vasculitis	Erythema induratum of Bazin (nodular vasculitis)
		Erythema nodosum leprosum
		Lucio phenomenon
		Neutrophilic lobular panniculitis

Predominantly Septal Panniculitis

Erythema Nodosum

Erythema nodosum (EN) is the best known of the various forms of panniculitis, as well as the most common. It can occur at any age, in both sexes, and in all racial groups, although it is more common among women during the second through fourth decades of life. It is widely regarded as a delayed hypersensitivity response to a variety of antigenic stimuli, including bacteria, viruses, and chemical agents, although the mechanisms of its development are complex. The relative ranking of underlying causes may vary according to geographic location, and a summarized list of the most common etiologies is outlined in Table 12-2 . However, more than one-third of cases of EN have no known disease association, even when followed over a long period of time. Moreover, although the exact pathogenesis of EN remains unknown, some evidence supports a circulating immune-complex-mediated pathogenesis. Clinically, patients often have serum-sickness-like signs and symptoms, such as fever, malaise, arthralgias, arthritis, and myalgias, features often associated with circulating immune-complex-mediated disease. EN usually presents as an acute eruption of tender, erythematous subcutaneous nodules over the bilateral pretibial areas ( Fig. 12-1 ), with other locations being occasionally involved, particularly the thighs and forearms. Unlike other forms of panniculitis, ulceration is not a feature of EN. The lesions usually last for a few days or weeks and then slowly involute, changing in color like an ecchymosis, and healing without scar formation. More chronic forms do occur, some of which show a tendency toward migration or centrifugal spread, referred to as subacute nodular migratory panniculitis or erythema nodosum migrans . This entity is believed by many authors to represent a variant of EN; however, others consider it to be a separate disorder. Untreated, subacute nodular migratory panniculitis can last for months to years.

TABLE 12-2

Etiology of Erythema Nodosum and Patient Evaluation

CAUSES	Common	Idiopathic
	Common	Common infectious associations: streptococcal infections, bacterial gastroenteritis ( Yersinia , Salmonella , Campylobacter ), viral upper respiratory tract infections, coccidioidomycosis
	Uncommon	Drugs (especially estrogens and oral contraceptive pills; also sulfonamides, penicillin, bromides, iodides; occasionally TNF inhibitors)
		Sarcoidosis
		Inflammatory bowel disease (Crohn’s disease > ulcerative colitis)
		Neutrophilic dermatoses (Behçet’s disease, Sweet’s syndrome)
		Pregnancy
		Uncommon infectious associations (brucellosis, Chlamydophila pneumoniae , C. trachomatis , Mycoplasma pneumoniae , tuberculosis, hepatitis B, histoplasmosis)
	Rare	Pernicious anemia, diverticulitis, malignancy (acute myelogenous leukemia, Hodgkin’s disease)
	Rare	Rare infectious associations: gonorrhea, meningococcemia, Escherichia coli , pertussis, syphilis, cat scratch disease, HIV infection, blastomycosis, giardiasis, multiple amebic abscesses
PATIENT EVALUATION	History	Drugs
		Exposure to infectious agents
		Symptoms of an infection
		Symptoms of bowel disease
	Physical examination
	Laboratory studies	Blood cell count, erythrocyte sedimentation rate, γ-globulin levels, urinalysis
		Skin test for tuberculosis
		Throat culture
		Anti-DNase B titer (for Streptococcus )
		Pregnancy test (in women of childbearing age)
	Other studies	Chest X-ray (to exclude tuberculosis, sarcoidosis, or deep fungal infection)