Erythema Nodosum and Erythema Induratum

Slide 1 · ERYTHEMA NODOSUM

AND

ERYTHEMA INDURATUM

Clinicopathologic comparison of two panniculitides

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Localize inflammation to subcutaneous septa or fat lobules.

Distinguish the clinical course of erythema nodosum from erythema induratum.

Interpret key histologic features, particularly vasculitis and necrosis.

Select a sufficiently deep biopsy and integrate systemic associations.

Slide 3 · Panniculitis is inflammation of the subcutis

Subcutaneous adipose tissue is the primary inflammatory compartment.

Inflammation may be centered on fat lobules or their connective-tissue septa.

This compartmental pattern is a starting point for histologic classification.

Schematic

Epidermis

Dermis

Subcutaneous adipose lobules (schematic)

Slide 4 · A fat lobule is separated by fibrous septa

Adipocytes form lobular aggregates within the subcutaneous layer.

Connective-tissue septa partition lobules and contain vessels.

Diagnosis requires enough subcutis to evaluate both compartments.

Schematic

Septa (blue)

Lobules (red foci)

Slide 5 · Septal and lobular patterns are not interchangeable

Septal panniculitis: Inflammation predominates between lobules.

Lobular panniculitis: Inflammation predominates inside lobules.

A mixed lesion requires identification of its dominant pattern.

Schematic

Septa (blue)

Lobules (red foci)

Slide 6 · Vasculitis is a second diagnostic axis

Classify the compartment: Septal versus lobular.

Assess whether vascular walls show inflammation and destruction.

The combination narrows the differential more than either feature alone.

Schematic

1. Compartment

Septal

Lobular

2. Vascular injury

Absent

Present

Slide 7 · Deep sampling determines whether the pattern is visible

A superficial sample may contain dermis but too little adipose tissue.

A deep wedge or incisional biopsy helps demonstrate septa, lobules, and vessels.

Inadequate sampling may misclassify panniculitis or overlook vasculitis.

Schematic

Narrow sample

Deep wedge samples fat

Slide 8 · Two diseases: One tissue, different primary patterns

Characteristic

Erythema nodosum

Erythema induratum

Dominant site

Fibrous septa

Fat lobules

Vasculitis

Classically absent

Deep necrotizing vasculitis

Necrosis

Not defining

Fat and sometimes caseous necrosis

Typical course

Bruise-like fading; no scar

Nodules often ulcerate

Slide 9 · Erythema nodosum: The prototypical septal panniculitis

Most common form of panniculitis in the Robbins account.

Usually has a subacute presentation involving the lower legs.

Its recognizable clinical and histologic signatures are complementary.

Schematic

Inflammation centered on interlobular septa

Slide 10 · A lesion may be easier to feel than to see

Poorly defined, erythematous plaques and nodules are characteristic.

Lesions are often deep enough to be identified by palpation.

Severe tenderness is a distinctive clinical clue.

Clinical recognition begins with palpation, not merely surface color.

Slide 11 · Lower-leg distribution is a major clue

Panniculitis often affects the lower legs.

Erythema nodosum commonly presents as tender nodules on the anterior shins.

Distribution increases suspicion but does not establish etiology.

Schematic

Typical lower-leg sites

Slide 12 · The pain reflects an inflamed deep compartment

Exquisite tenderness is a prominent feature of erythema nodosum.

The palpable nodule is located in inflamed subcutaneous tissue.

A normal-looking overlying surface does not exclude substantial pathology.

Interpret this as a clinicopathologic relation; It is not a validated pain mechanism.

Slide 13 · Constitutional symptoms may accompany skin findings

Fever and malaise can accompany the eruption.

Skin lesions may therefore signal a process beyond the skin.

Clinical history should search for systemic and exposure-related clues.

Slide 14 · Erythema nodosum has several categories of association

Infections, medication exposure, and systemic inflammatory disease.

Some malignant neoplasms also occur in association.

An etiologic association is not the same as a proven cause in an individual.

Schematic

Infections

Drugs

Inflammatory diseases

Neoplasms

No identified cause

Slide 15 · Streptococcal infection is a recognized association

β-hemolytic streptococci among triggers.

A recent history of pharyngitis or infection can guide evaluation.

Document chronology before attributing the eruption to an infection.

Slide 16 · Tuberculosis and selected deep infections are relevant

Infectious group

Examples in Robbins

Interpretation

Commonly highlighted

β-hemolytic streptococci; tuberculosis

Investigate when relevant

Less common

Coccidioidomycosis; histoplasmosis

Context/exposure dependent

Other

Leprosy

Clinical and epidemiologic context

Slide 17 · Medication exposure belongs in the history

Sulfonamides are among the textbook-listed drug associations.

Oral contraceptives are also specifically cited.

Time of initiation and cessation helps evaluate plausibility.

Schematic

Exposure / medication

Immune reaction suspected

Septal inflammation

Slide 18 · Sarcoidosis is an important systemic association

Sarcoidosis can be accompanied by erythema nodosum.

The panniculitis pattern does not itself identify the systemic disorder.

Investigate systemic manifestations when the clinical setting suggests them.

Slide 19 · Inflammatory bowel disease is another association

Inflammatory bowel disease is specifically listed.

Gastrointestinal history may provide a useful etiologic clue.

The skin lesion alone cannot distinguish the underlying bowel condition.

Slide 20 · Malignancy is a possible but nonspecific association

Certain malignant neoplasms among associations.

No specific tumor type or screening threshold is provided in this section.

Avoid implying cancer when the clinical evaluation does not support it.

Slide 21 · Many cases remain without an identified trigger

The chapter explicitly notes that a cause often cannot be found.

A negative etiologic work-up does not automatically refute the morphology.

Separate the diagnosis of panniculitis from certainty about its trigger.

Schematic

Name the tissue pattern

Review clinical associations

Cause may remain undetermined

Slide 22 · Delayed hypersensitivity is the proposed mechanism

A proposed delayed response to microbial or drug antigens.

This is a mechanistic hypothesis, not a demonstrated pathway in every patient.

Different initiating antigens may converge on a similar septal pattern.

Schematic

Microbial / drug antigen

Proposed delayed immune response

Septal inflammatory reaction

Slide 23 · Immune complexes have been implicated in some cases

Immune complex participation is reported for a subset of cases.

Its presence should not be assumed for every lesion.

The account explicitly emphasizes that pathogenesis is mostly unresolved.

Schematic

Clinical antigen exposure

Immune complexes: Proposed in some

Most cases: Pathway uncertain

Slide 24 · The same morphology does not prove the same trigger

Different exposures and systemic diseases can be associated with nodules.

The reaction pattern summarizes tissue injury, not a single pathogen.

Etiologic attribution requires clinical evidence outside the skin specimen.

Slide 25 · Erythema nodosum changes over weeks

Inflamed tender nodules gradually flatten.

Resolving lesions take on a bruise-like appearance.

New lesions may emerge while older ones are regressing.

Schematic

Tender red nodule

Gradual flattening

Bruise-like fading

No scar

Evolution over weeks; Not a measured time scale

Slide 26 · Bruise-like fading is a useful evolution clue

Early: Erythematous tender plaques or nodules.

Later: Flattening and bruise-like discoloration.

An isolated mature lesion may look different from a newly erupted one.

Schematic

Inflamed / red

Flattening

Bruise-like

Resolved

Evolution over weeks; Not a measured time scale

Slide 27 · Individual nodules usually resolve without scarring

Resolution without residual scar.

The absence of ulcerative tissue destruction helps contrast erythema induratum.

Interpret the overall eruption over time, not just a single observation.

Schematic

Erythema nodosum

Erythema induratum

Tender nodules

Bruise-like fading

No residual scar

Slightly tender nodule

Vascular necrosis

Often ulcerates

Slide 28 · Crops can overlap in time

New nodules may develop while older nodules flatten.

A patient can have lesions at different stages simultaneously.

Biopsy interpretation should take the lesion’s age into account.

Schematic

New nodule A

Lesion A fades

New nodule B

Overlapping crops

Different lesions may have different ages

Slide 29 · Histology: The earliest finding is septal expansion

Early erythema nodosum widens the fibrous septa.

Edema is a principal reason for the increase in septal thickness.

The predominant anatomic center remains interlobular connective tissue.

Schematic

Early: Edematous widened septa

Slide 30 · Fibrinous exudate accompanies early inflammation

Fibrin exudation in early lesions.

Interpret fibrin in the context of edematous inflamed septa.

Do not confuse septal exudation with necrotizing vascular injury.

Slide 31 · Early erythema nodosum is often neutrophil rich

Neutrophilic infiltration is an early histologic component.

A neutrophil-rich septum must be evaluated with the lesion age in mind.

Superficial or very early sampling can obscure the complete pattern.

Schematic

Neutrophils concentrated along septa

Slide 32 · The infiltrate changes as lesions mature

Lymphocytes and macrophages become prominent later.

Multinucleated giant cells may accompany the later response.

Occasional eosinophils are described in the chapter.

Schematic

Later: Mononuclear + giant-cell response

Slide 33 · Septal fibrosis marks a later stage

Later lesions show fibrosis within the affected septa.

Inflammatory composition changes alongside connective-tissue remodeling.

The histology of a late nodule should not be expected to mimic a fresh one.

Schematic

Late: Collagenous septal thickening

Slide 34 · Classic erythema nodosum lacks necrotizing vasculitis

, vasculitis is absent in the characteristic morphology.

This is a powerful contrast with erythema induratum.

Pathology reporting should specify vascular-wall findings rather than use vague “inflammation” terminology.

Schematic

Vessel lumen

Intact vessel wall

Slide 35 · Miescher radial granulomas: A supplementary clue

Small histiocyte aggregates may form around a central cleft in septa.

They support an erythema-nodosum pattern when present.

Published reviews caution that they are not absolutely pathognomonic.

Schematic

Schematic radial histiocyte aggregate

Slide 36 · A lesion’s age determines what the pathologist sees

Feature

Early erythema nodosum

Later erythema nodosum

Septa

Edematous and widened

Fibrotic and thickened

Inflammatory cells

Neutrophils prominent

Lymphocytes; macrophages; giant cells

Additional elements

Fibrin exudation

Occasional eosinophils

Vasculitis

Classically absent

Classically absent

Slide 37 · Clinical diagnosis and biopsy answer different questions

Clinical history establishes distribution, tenderness, and time course.

Deep histology localizes inflammation and assesses vessel injury.

History and targeted testing help assign a possible underlying trigger.

Schematic

Clinical course

Deep morphology

Etiologic context

Slide 38 · A directed etiologic evaluation is preferable

Review recent infection, drug exposure, and systemic inflammatory symptoms.

Investigations are guided by risks and findings, not a universal test panel.

Examples in clinical reviews: Inflammatory markers, streptococcal testing, TB assessment or chest imaging when indicated.

Slide 39 · Do not treat a clinical association as histologic proof

An erythema-nodosum biopsy does not identify streptococci, sarcoidosis, or IBD.

The same septal pattern can arise across multiple clinical contexts.

Reports should state the morphologic diagnosis and separately note clinical correlations.

Slide 40 · Erythema induratum: An uncommon vasculitic panniculitis

It as an uncommon form of panniculitis.

Its characteristic target is the deep vascular supply of subcutaneous fat.

Vascular compromise leads to fat necrosis and inflammation.

Schematic

Deep arterial/venous injury

Compromised fat perfusion

Fat necrosis + inflammation

Slide 41 · Population pattern is descriptive, not diagnostic

Adolescents and menopausal females.

Demographic patterns cannot replace tissue diagnosis.

In a compatible lesion, consider the disease beyond a strict age group.

Slide 42 · The clinical nodule is less exquisitely tender

Erythema induratum presents as an erythematous nodule.

It is typically described as slightly tender, compared with intense tenderness in erythema nodosum.

Depth and ulceration are more discriminating than redness alone.

Slide 43 · Ulceration strongly shifts the differential

Erythema-induratum nodules usually ulcerate.

Erythema nodosum typically fades without a residual scar.

An ulcerating deep nodule warrants assessment for vascular injury or another destructive process.

Schematic

Ulcerated surface over inflamed fat

Slide 44 · The proposed initiating event is deep-vessel vasculitis

Erythema induratum as primarily vascular in origin.

Deep vessels supplying the subcutaneous fat lobules are involved.

The early vascular lesion helps explain subsequent parenchymal injury.

Schematic

Vessel lumen

Wall injury + inflammatory cells

Slide 45 · Vascular injury compromises lobular perfusion

Damage to deep vessels can reduce blood supply to the surrounding fat.

Fat necrosis and an inflammatory response follow vascular compromise.

This pathogenesis is a textbook interpretation, not a universally proved initiating sequence.

Schematic

Deep arterial/venous injury

Compromised fat perfusion

Fat necrosis + inflammation

Slide 46 · Fat-lobule injury produces the lobular pattern

Erythema induratum is centered on the adipose lobules.

The accompanying inflammatory reaction differs from primarily septal erythema nodosum.

Map the affected fat compartment before evaluating individual cell types.

Schematic

Inflammation within adipose lobules

Slide 47 · Granulomatous inflammation is characteristic

Granulomatous reaction involves the fat lobules.

The histologic pattern reflects a macrophage-rich inflammatory response.

The pattern is not by itself a specific microbiologic diagnosis.

Schematic

Granulomatous inflammation within fat

Slide 48 · Caseous necrosis is described within fat lobules

Zones of caseous necrosis in erythema induratum.

This finding must be interpreted alongside granulomas and vascular injury.

Caseation alone cannot establish active tuberculosis in a skin biopsy.

Schematic

Lobular necrosis with inflammatory response

Slide 49 · Early vessel changes affect arteries and veins

Small- to medium-sized arteries and veins may show necrotizing vasculitis.

Affected vessels lie in the deep dermis and subcutis.

Both the caliber and anatomical level of involved vessels matter.

Schematic

Vessel lumen

Wall injury + inflammatory cells

Slide 50 · Tuberculosis: Historical association, variable today

Erythema induratum was originally considered a hypersensitivity response to tuberculosis.

Cases now commonly lack identifiable underlying disease.

Clinical evidence is needed to determine whether tuberculosis is implicated.

Schematic

Historical concept

Tuberculosis hypersensitivity

Modern cases may lack a known systemic association

Slide 51 · Nodular vasculitis and erythema induratum: Terminology

Term

Common contemporary usage

Diagnostic caution

Erythema induratum of Bazin

Tuberculosis-associated nodular vasculitis

Requires clinical association

Nodular vasculitis

Similar deep vasculitic panniculitis without proven TB

Not defined by biopsy alone

Erythema induratum (Robbins)

Broader clinical-pathologic entity

Historical usage overlaps

Slide 52 · Tuberculosis assessment is contextual

Clinical history, local epidemiology, exposure, and systemic findings guide assessment.

TB testing or chest investigations may be appropriate in a compatible setting.

Negative organism stains in skin do not alone establish or refute a TB-associated process.

Slide 53 · The diagnostic contrast begins at low power

Low-power clue

Erythema nodosum

Erythema induratum

Primary compartment

Septa

Lobules

Architecture

Widened septa; later fibrosis

Lobular inflammation and fat necrosis

Vascular involvement

Classically no destructive vasculitis

Early deep necrotizing vasculitis

Granulomatous element

May have giant cells / radial nodules

Granulomatous lobular reaction

Slide 54 · Early and late biopsies tell different stories

Early erythema nodosum: Edema, fibrin, neutrophils in septa.

Later erythema nodosum: Mononuclear infiltrate and septal fibrosis.

Early erythema induratum: Necrotizing deep-vessel inflammation; Lobular necrosis and granulomas are also key features.

Schematic

Early EN: Edema

Early EN: Neutrophils

Later EN: Fibrosis

EI: Deep vascular injury

Compare lesion age and vascular pattern

Slide 55 · A practical classification pathway

First: Confirm a subcutaneous inflammatory lesion.

Second: Distinguish septal from lobular predominance.

Third: Evaluate deep vessels, necrosis, and granulomatous reaction.

Finally: Integrate site, ulceration, timing, and clinical associations.

Schematic

Deep inflamed subcutis

Septal or lobular?

Vasculitis / necrosis?

Correlate clinical course

Slide 56 · When the biopsy is too shallow, diagnosis suffers

Little or no subcutis prevents confident compartment assignment.

Deep vasculitis may lie below the sampled dermis.

A nondiagnostic superficial sample is not equivalent to a negative panniculitis evaluation.

Schematic

Shallow: Dermis only

Deep wedge samples fat

Slide 57 · Other panniculitides are meaningful differentials

Mimic from adjacent section

Why it matters

Factitial panniculitis

Trauma/injection can cause secondary inflammation

Lupus-associated panniculitis

Systemic autoimmunity may involve subcutis

Subcutaneous T-cell lymphoma

Neoplastic cells can mimic fat inflammation

Weber–Christian disease

Separate lobular, nonvasculitic pattern

Slide 58 · Case 1: Acute, exquisitely tender lower-leg nodules

ILLUSTRATIVE CASE

A patient develops multiple painful erythematous nodules on the shins.

Over subsequent weeks, earlier nodules flatten and become bruise-like.

What compartment and vascular pattern would best fit?

Slide 59 · Case 1: Expected histologic pattern

Septal widening with edema and early neutrophilic inflammation.

Evolving lesions may show lymphocytes, macrophages and septal fibrosis.

Classic pattern: No necrotizing vasculitis.

Schematic

Septa (blue)

Lobules (red foci)

Most likely pattern: Erythema nodosum.

Slide 60 · Case 2: A deep nodule progresses to ulceration

ILLUSTRATIVE CASE

A slightly tender lower-leg nodule becomes ulcerated.

Deep biopsy shows fat-lobule inflammation and necrosis.

What additional histologic feature is especially discriminating?

Slide 61 · Case 2: Inspect the deep arterial and venous walls

Necrotizing vasculitis in small- and medium-sized deep vessels supports the pattern.

Lobular granulomatous inflammation and caseous necrosis may coexist.

Then assess whether an underlying TB association can be established clinically.

Schematic

Vessel lumen

Wall injury + inflammatory cells

Most likely pattern: Erythema induratum / nodular vasculitis.

Slide 62 · Case 3: A source-identification pitfall

ILLUSTRATIVE CASE

A biopsy shows classic erythema-nodosum morphology.

The patient reports no recent drug exposure or infectious symptoms.

The histology supports a reaction pattern, not a specific trigger.

An unidentified cause remains compatible with the Robbins account.

Slide 63 · Report the morphology before speculating on etiology

State dominant compartment: Septal, lobular, or mixed.

Describe inflammation, fat necrosis, granulomatous change, and vessel injury.

Note sample depth and lesion-age limitations if relevant.

Reserve etiologic claims for an integrated clinical assessment.

Schematic

Anatomic compartment

Cellular pattern + necrosis

Vessel-wall injury

Adequacy + clinicopathologic correlation

Slide 64 · Integrated comparison: Clinical and microscopic

Question

Erythema nodosum

Erythema induratum

Pain

Often exquisitely tender

Often slightly tender

Surface evolution

Bruise-like fading

Frequently ulcerates

Primary inflammation

Septa

Fat lobules

Deep vessels

No classic vasculitis

Necrotizing vasculitis

Late / associated change

Septal fibrosis

Granulomas; caseous necrosis

Slide 65 · Three practical decisions

Recognize the clinical pattern and lesion evolution.

Sample deep enough to include representative septa, lobules, and vessels.

Integrate the biopsy reaction pattern with possible systemic associations.

Schematic

Clinical course

Deep morphology

Etiologic context

Slide 66 · Selected sources and further reading

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026).

DermNet. Erythema nodosum (2019 update); Erythema nodosum pathology (2015).

DermNet. Nodular vasculitis (2008; accessed 2026).

Pérez-Garza DM et al. Erythema Nodosum: A Practical Approach and Diagnostic Algorithm. Am J Clin Dermatol. 2021;22:367–378.

Sánchez Yus E et al. Miescher’s radial granuloma: a characteristic marker of erythema nodosum. Am J Dermatopathol. 1989;11:434–442.