Transcript Erythema Nodosum

PANNICULITIS
Gentleman’s Review
Daniel Martingano OMSII
PANNICULITIS
Definition
• Panniculitis is a group of heterogenous
inflammatory diseases affecting primarily the
subcutaneous adipose tissue.
• These disorders have been classically considered
diagnostically challenging, both for dermatologists
and pathologists, for several reasons.
Septal and Lobular Panniculitis
• The pathologists classify the panniculitic process as a
mostly septal or a mostly lobular panniculitis, and this
classification system is very helpful for initial
diagnostic purposes.
• However, this step is just the first one in the diagnostic
process, and it should be followed by the search for
additional histopathologic findings that allow for a
more specific final diagnosis in the language of clinical
dermatology.
Histology of the Subcutaenous
Tissue
• The basic unit of the subcutaneous tissue is the
primary microlobule, which measures approximately 1
mm in diameter and is composed of a microscopic
collection of adipocytes.
• Primary microlobules aggregate to form secondary
lobules that measure approximately 1 cm in diameter
and are surrounded by thin septa of connective tissue.
ERYTHEMA NODOSUM
Definition
• Erythema nodosum is the most frequent clinicopathologic variant of
panniculitis and is the paradigm of predominantly septal panniculitis.
• The disorder usually exhibits an acute onset and is clinically
characterized by the sudden eruption of erythematous tender
nodules and plaques located predominantly over the extensor
aspects of the lower extremities.
• The lesions show spontaneous regression, without ulceration,
scarring, or atrophy, and recurrent episodes are not uncommon.
Clinical Presentation
ERYTHEMA NODOSUM
Erythematous Nodules
• The typical eruption is quite characteristic and consists
of a sudden onset of symmetrical, tender, warm,
raised erythematous nodules usually located on the
shins, ankles and knees.
• The nodules, which range from 1 to 5 cm or more in
diameter, are usually bilaterally distributed.
– Nodules may become confluent resulting in erythematous
plaques.
Characteristic Color Evaluation
• At first, the nodules show a bright red color and are raised
slightly above the skin.
– Lesions change color in the second week from bright red to
bluish or livid.
• As absorption progresses, the color gradually fades to a
yellowish or greenish hue, resembling a bruise.
– This color evolution is quite characteristic of erythema nodosum
and allows a specific diagnosis in late stage lesions.
Healing
• Ulceration and suppuration are never seen
in erythema nodosum and the nodules
heal without atrophy or scarring.
General Symptoms
• Usually acute bouts of erythema nodosum are
associated with a fever of 38 to 39°C (100-102°F),
fatigue, malaise, arthralgia, headache, abdominal
pain, vomiting, cough, or diarrhea.
• Arthralgia occurs in more than 50% of patients and
begins during the eruptive phase or precedes the
eruption by 2-4 weeks.
General Symptoms
• Erythema, swelling, and tenderness occur over the
joint, sometimes with effusions.
• Any joint may be involved, but the ankles, knees, and
wrist are affected most commonly. Synovitis resolves
within a few weeks.
– No destructive joint changes occur.
– Synovial fluid is acellular, and the rheumatoid factor is
negative.
Laboratory Studies
• The white blood count is normal or only slightly
increased, but the erythrocyte sedimentation rate
is often very high, returning to normal when the
eruption fades.
• The rheumatoid factor is usually negative, and
there is a temporary increase in the alpha2globulin.
Laboratory Studies
• A high antistreptolysin O titer is seen in
those cases of erythema nodosum
associated with a sore throat streptococcal
infection.
Etiology
ERYTHEMA NODOSUM
Streptococcal Infections
• The relationship between a previous episode of upper
respiratory tract infection by group A β-hemolytic
streptococcus and erythema nodosum is well-known,
especially in children and young adults.
– Usually, the cutaneous lesions appear 2 or 3 weeks after the
throat infection, and they are accompanied by an elevation of the
antistreptolysin O (ASO) titer.
• When the cutaneous nodules develop, the cultures of routine
throat swabs usually do not detect microorganisms.
Tuberculosis
• Tuberculosis is now an uncommon etiologic
factor for erythema nodosum.
• These cases are seen mostly in children, and
the cutaneous lesions of erythema nodosum
usually indicate a primary pulmonary infection
Drugs
• Sulfonamides and oral contraceptive pills have been
long recognized as the most common medications
responsible for acute bouts of erythema nodosum, but
the list of possibilities is very large.
• In those cases in which the patient develops erythema
nodosum when is taken an antibiotic for an infectious
disease is difficult to discern whether the cutaneous
reaction is due to the antibiotic or the infectious agent.
Sarcoidosis
• Sarcoidosis constitutes one of the most common
etiologic factors in adult patients with secondary
erythema nodosum.
• In northern Europe, erythema nodosum and
bilateral hilar adenopathy frequently are seen as
early manifestations of sarcoidosis (Löfgren
syndrome).
Inflammatory Bowel Disease
• In adults, erythema nodosum associated with
enteropathies often correlates with a flare-up of
the disease, although the cutaneous eruption may
precede the clinical appearance of the
inflammatory bowel disease.
• Ulcerative colitis is more frequently associated
with erythema nodosum than Crohn disease
Malignancy
• Erythema nodosum may be a cutaneous
marker of malignancy, most often
lymphoma or leukemia.
Pathogenesis
• Erythema nodosum is considered to be a
type IV, delayed hypersensitivity response to
a wide variety of inciting factors.
• Histopathologic features in fully developed
lesions suggest a delayed hypersensitivity
mechanism.
Pathology
ERYTHEMA NODOSUM
Early Stage Lesions
• The composition of the inflammatory infiltrate in the
septa varies with age of the lesion. In early lesions,
edema, hemorrhage, and neutrophils are responsible
for the septal thickening.
• Late stage lesions in the septa are characterized by
fibrosis, periseptal granulation tissue, lymphocytes,
histiocytes, and multinucleated giant cells.
Meischer Radial Granulomas
• In the early stage of erythema nodosum, two histopathologic
lesions are prominent:
– septal infiltration with abundant numbers of neutrophils;
– Miescher radial granulomas.
• Miescher radial granulomas are a histopathologic hallmark of
erythema nodosum.
– They consist of small, well-defined nodular aggregations of small
histiocytes around a central stellate or banana shaped cleft.
Meischer Radial Granulomas
• Miescher radial granulomas are present in all stages
of the evolution of erythema nodosum lesions.
•
In early lesions, Miescher radial granulomas appear
scattered in the septa and surrounded by neutrophils.
• In older nodules of erythema nodosum, histiocytes
coalesce to form multinucleated giant cells.
Absence of Vasculitis
• Another histopathologic characteristic of
erythema nodosum is the absence of
vasculitis.
Late Stage Lesions
• In late stage lesions of erythema nodosum, the
inflammatory infiltrate in the septa is sparse, and there
are markedly widened septa with granulation tissue at
the interface between connective tissue septa and fat
lobules.
• As erythema nodosum evolves, the septa become
fibrotic and replaced by granulomas containing
multinucleated giant cells.
Late Stage Lesions
• The fat lobules become progressively replaced and effaced by
widening septa, which can even completely obliterate the lobules.
• In these late lesions may be difficult to establish whether the lesion
is a mostly septal or mostly lobular panniculitis, because the entire
subcutaneous tissue is effaced by a fibrotic and granulomatous
process.
• With time, despite the striking fibrosis, the lesions resolve without
atrophy or scarring of the involved septa.
ERYTHEMA INDURATUM
Definition
• Erythema induratum of Bazin (EIB) is a chronic,
nodular eruption that usually occurs on the lower
legs of young women.
• Erythema induratum is regarded as a
manifestation of type IV delayed hypersentivitity
reaction to Mycobacterium tuberculosis.
Definition
• Patients with erythema induratum have a
positive tuberculin skin test result and a
marked increase in their peripheral T
lymphocyte response to purified protein
derivative (PPD) of tuberculin,
– which causes a delayed-type hypersensitivity
reaction against molecular fragments of
tuberculosis bacilli.
Clinical Presentation
• 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, are more persistent, often ulcerate, and
regress leaving an atrophic scar.
Clinical Presentation
• On physical examination, crops of small, tender,
erythematous nodules are observed.
– These nodules are concentrated on the lower third of the
legs, especially around the ankles.
• Often subcutaneous nodules become adherent to the
skin surface and ulcerate. Healing of these ulcers is
usually a slow process, resulting in atrophic scars.
Clinical Presentation
• The course is protracted and recurrent episodes
over years, even decades, are common.
• Individual lesions tend to involute, but new crops
appear at irregular intervals. Patients with
erythema induratum of Bazin are otherwise in
good health.
Laboratory Studies
• Peripheral blood cell count and complete
metabolic panel are normal.
• Erythrocyte sedimentation rate is elevated.
Pathology
ERYTHEMA INDURATUM
Erythema Induratum of Bazin
• In contrast to erythema nodosum, which is mainly septal
panniculitis, erythema induratum initially is mainly a
lobular panniculitis due to vasculitis that produces
ischemic necrosis of the fat lobule with relatively less
involvement of the structures of the septa.
Vasculitis
• The presence of vasculitis in the biopsy specimen
is not always identified and is not considered a
requisite for making the diagnosis.
• At the septae, a vasculitis of small and middle size
vessels can be seen, sometimes affecting the
muscular arteries with fibrinoid necrosis and
hemorrhage.
Topography of Vascular
Necrosis
• Vascular architecture of subcutaneous tissue explains the
intralobular localization of necrosis.
• Each individual secondary lobule is supplied by a small
muscular artery branching from the septa to form arterioles
that supply every individual primary microlobule.
• The arterioles branch to form capillaries into the microlobule
and a capillary network surrounds each individual adipocyte.
Topography of Vascular
Necrosis
• Postcapillary venules meet in veins, which also
run along the septa. In each microlobule, the
arteriole occupies a central position, whereas the
venule runs along the periphery.
• As a consequence, interference with the arterial
supply results in diffuse necrosis within the fat
lobule (lobular panniculitis).
Lobular Histopathologic
Changes
• At an early stage, the fat lobules are punctuated
throughout by discrete collections of inflammatory
cells, mostly neutrophils.
• There may be extensive necrosis of the
adipocytes of the fat lobule (fat necrosis).
– These necrotic adipocytes call for histiocytes that
ingest lipid and become foamy.
Lobular Histopathologic
Changes
• Later a second type of necrosis, caseous necrosis, develops.
Epithelioid cells, multinucleated giant cells, and lymphocytes
contribute to the granulomatous appearance of the inflammatory
infiltrate in fully developed lesions of erythema induratum of Bazin.
• When intense vascular damage is present, extensive areas of
caseous necrosis become extensive.
• Caseous necrosis may extend to the overlying dermis and
secondarily involve the epidermis with ulceration and discharge of
liquefied necrotic fat.
Ziehl-Neelsen Stain
• Ziehl-Neelsen stain (which is used to visualize acidfast bacilli) does not reveal intact mycobacteria.
• In one third of cases granulomas are absent and
lymphocytes and plasma cells predominate.
• Both the tuberculoid granulomas and lymphoid
infiltrate extend between the fat cells, largely replacing
them.