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APPROACH TO
ERYTHEMA NODOSUM
DR A P Naveen Kumar
Chief Specialist ( General Medicine )
Visakha Steel General Hospital
Visakhapatnam
INTRODUCTION
PATHOPHYSIOLOGY
 Delayed hypersensitivity reaction to a variety of
antigens
 CIC have not been found in idiopathic or
uncomplicated cases
 IBD – may show immune complexes
HISTOLOGIC FINDINGS
 Septal panniculitis -septal
edema and lymphohistiocytic
infiltrate
 Miescher’s microgranulomas -
clusters of macrophages
around small vessels or a slit-
like space
 Lymphohistiocytic infiltrate
 Granuloma and lipogranuloma
formation
CLINICAL FEATURES
 Erythema nodosum usually starts
with flu-like symptoms of fever and
bodyaches
 Arthralgia may precede the
eruptive phase
 Red tender nodules usually on the
anterior surface of legs-shins
 Other areas- arms, trunk and face
 Lesions borders are poorly
defined and vary from
2 cm to 10 cm
 1 st week - tense, hard,
red and painful
 2nd week - fluctuate and attain a
yellowish hue, resembling a bruise
 Do not suppurate or ulcerate
 Individual lesions usually last for 2
weeks but occasionally new lesions
appear up to 3–6 weeks
 Lesions disappear as the overlying
skin desquamates
 Joint tenderness and morning stiffness
may occur.
 No destructive changes occur.
Synovial fluid is acellular and
rheumatoid factor (RF) negative
INFECTIONS
 Streptococcal
 Tuberculosis
 Deep fungal infections
 Coccidiodomycosis (4–10%)
 Yersinia enterocolitis
 Cryptococcus
 Rickettsia
Histoplasmosis
Blastomycosis
Infectious mononucleosis
Mycoplasma
Salmonella
Campylobacter
Lymphogranuloma venereum
Parasitic diseases
DRUGS
 Sulfonamides
 OCP
 Sulfonylureas
 Gold
 Penicillins
 Iodides
 Bromides
 Phenytoin
 Minocycline
SYSTEMIC DISEASES
 Sarcoidosis (10–22%)
 Inflammatory bowel disease
 Leprosy
 Pregnancy
 Behçet disease
 NHL
 AML
STREPTOCOCCAL PHARYNGITIS
 Beta-hemolytic streptococcal infections- most common
 44% - adults and 48% - in children
 EN eruptions-2–3 weeks after an episode of streptococcal
pharyngitis
 Should have throat culture evaluation for group A strep.,
as well as strep. antistreptolysin O (ASO) titers or
polymerase chain reaction (PCR) assays, or both
 ASO titers should be taken at the time of diagnosis and
then again within 4 weeks to assess for strep. infection
TUBERCULOSIS AND
MYCOBACTERIAL INFECTIONS
 Erythema nodosum may occur with primary TB
 All patients with EN should be stratified by risk for TB
exposure
 Antitubercular therapy (ATT) should be initiated for EN in
patients with positive Mantoux skin test reactions
 Culture identification from primary sites identifying an
atypical nontuberculous mycobacterium as a cause of EN.
Nodule
Multiple
granulomas
Granuloma
Epitheloid granuloma with necrosis
LABORATORY DIAGNOSIS
 Careful history, physical examination and drug history
 Prior diarrheal illness, URTI and any endemic infections
 Throat culture—rules out streptococcal infection
 CBC and ESR
 Antistreptolysin O (ASO)/DNase titer at 2 weeks and 4 weeks interval
 Stool examination.
 Chest X-ray (CXR)— purified protein derivative (PPD) to rule out
Koch’s, unilateral hilar lymph nodes—Infections and malignancy
 CXR to rule out sarcoid—bilateral hilar lymph nodes
 Biopsy the lesion to rule out vasculitis—Collagen vascular disease.
DIFFERENTIAL DIAGNOSIS
 Lupus panniculitis—present in fatty areas such as
buttocks, posterior arms and leave scars
 Tuberculous erythema induratum—usually ulcerate
 Erythema nodosum leprosum
 Acute urticaria—itching is intense
 Nodular vasculitis-PAN—look for fixed livedo reticularis
 Sarcoidosis
 Superficial thrombophlebitis—linear tender streaks
 Erysipelas
 Filarial lymphadenitis
 Insect bites.
SARCOID
IBD
APLA
Lupus anticoagulant positive
Anti Cardiolipin antibodies -positive
CHRONIC ERYTHEMA NODOSUM
 Chronic EN is a condition in which the lesions pop up
elsewhere for a period of weeks to months
 In most of the cases a cause is elusive
 TB should be considered in our settings and a trial ATT may
be given
 Intense investigations to rule out sarcoid, IBD and collagen
vascular disease (CVD) should be done
 Rare association- Takayasu arteritis, vitamin B12 deficiency
and Ehlers Danlos has been reported.
RECURRENT EN
THERAPEUTIC LADDER FOR EN
 Discontinue possible causative medications
 Treatment of underlying infectious diseases mainly
streptococcal and TB
 Bed rest and leg elevation and nonsteroidal anti-
inflammatory drugs (NSAIDs) (aspirin, ibuprofen,
indomethacin, naproxen)
 Potassium iodide—saturated solution of potassium
iodide-5–15 drops three times a day. Mechanism of
action is exactly not known
 Colchicine in the setting of Behçet’s disease
 Various treatments for IBD like systemic steroids, HCQS, MMF,
cyclosporine, thalidomide, infliximab and etanercept are effective in
managing the underlying EN
 Paradoxically both infliximab and etanercept have been reported to
produce EN as a cutaneous side effect.
 NSAID are to be avoided in IBD as they aggravate the disease
 Systemic steroids - relatively safe therapeutic option if underlying
infection, risk of bacterial dissemination or sepsis and malignancy has
been excluded by a thorough evaluation
 A general rule is 1 mg/kg (body weight)/day.
USE OF POTASSIUM IODIDE
 Saturated solution of potassium iodide 1,000 mg/mL
 Droppers - for calibrations: 0.3 mL (300 mg),0.6 mL ( 600 mg)
 In adults and older children, common dose = 300 mg TDS with starting
dose = 150–300 mg TDS
 Saturated solution of potassium iodide (SSKI)- bitter taste – water or
fruit juice
 Crystallization in cold - rewarming and shaking
 Discard if solution turns yellow-brown
Side effects: Acute—nausea, eructations, excessive salivation,
urticaria, angioedema, small vessel vasculitis
 Chronic—enlargement of salivary and lacrimal glands, acneiform
eruptions, iododerma, hypothyroidism, hyperkalemia and occasionally
hyperthyroidism
PROGNOSIS
 Erythema nodosum prognosis is excellent
 The lesions resolve without any adverse reactions
in most cases
 Few cases are recurrent and refractory for which
an underlying cause is to be ascertained and
treated accordingly
 Some of the idiopathic cases respond to
colchicine/dapsone on prolonged treatment.
CONCLUSIONS
 Erythema nodosum is an acute panniculitis
presenting as subcutaneous nodules most
commonly due to infections and responds well to
treatment
 Chronic nodules need to be investigated
thoroughly and treated accordingly.
ACKNOWLEDGEMENTS
 Dr Mala Saranathan ,Dermatologist
 Dr G Srihari , Dermatologist
 Dr M Srinivas , Pathologist
 Dr M Santipriya , Pathologist
Erythema nodosum

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Erythema nodosum

  • 1. APPROACH TO ERYTHEMA NODOSUM DR A P Naveen Kumar Chief Specialist ( General Medicine ) Visakha Steel General Hospital Visakhapatnam
  • 3.
  • 4. PATHOPHYSIOLOGY  Delayed hypersensitivity reaction to a variety of antigens  CIC have not been found in idiopathic or uncomplicated cases  IBD – may show immune complexes
  • 5. HISTOLOGIC FINDINGS  Septal panniculitis -septal edema and lymphohistiocytic infiltrate  Miescher’s microgranulomas - clusters of macrophages around small vessels or a slit- like space  Lymphohistiocytic infiltrate  Granuloma and lipogranuloma formation
  • 6. CLINICAL FEATURES  Erythema nodosum usually starts with flu-like symptoms of fever and bodyaches  Arthralgia may precede the eruptive phase  Red tender nodules usually on the anterior surface of legs-shins  Other areas- arms, trunk and face  Lesions borders are poorly defined and vary from 2 cm to 10 cm  1 st week - tense, hard, red and painful
  • 7.  2nd week - fluctuate and attain a yellowish hue, resembling a bruise  Do not suppurate or ulcerate  Individual lesions usually last for 2 weeks but occasionally new lesions appear up to 3–6 weeks  Lesions disappear as the overlying skin desquamates  Joint tenderness and morning stiffness may occur.  No destructive changes occur. Synovial fluid is acellular and rheumatoid factor (RF) negative
  • 8.
  • 9. INFECTIONS  Streptococcal  Tuberculosis  Deep fungal infections  Coccidiodomycosis (4–10%)  Yersinia enterocolitis  Cryptococcus  Rickettsia Histoplasmosis Blastomycosis Infectious mononucleosis Mycoplasma Salmonella Campylobacter Lymphogranuloma venereum Parasitic diseases
  • 10. DRUGS  Sulfonamides  OCP  Sulfonylureas  Gold  Penicillins  Iodides  Bromides  Phenytoin  Minocycline
  • 11. SYSTEMIC DISEASES  Sarcoidosis (10–22%)  Inflammatory bowel disease  Leprosy  Pregnancy  Behçet disease  NHL  AML
  • 12. STREPTOCOCCAL PHARYNGITIS  Beta-hemolytic streptococcal infections- most common  44% - adults and 48% - in children  EN eruptions-2–3 weeks after an episode of streptococcal pharyngitis  Should have throat culture evaluation for group A strep., as well as strep. antistreptolysin O (ASO) titers or polymerase chain reaction (PCR) assays, or both  ASO titers should be taken at the time of diagnosis and then again within 4 weeks to assess for strep. infection
  • 13.
  • 14. TUBERCULOSIS AND MYCOBACTERIAL INFECTIONS  Erythema nodosum may occur with primary TB  All patients with EN should be stratified by risk for TB exposure  Antitubercular therapy (ATT) should be initiated for EN in patients with positive Mantoux skin test reactions  Culture identification from primary sites identifying an atypical nontuberculous mycobacterium as a cause of EN.
  • 15.
  • 17.
  • 18. LABORATORY DIAGNOSIS  Careful history, physical examination and drug history  Prior diarrheal illness, URTI and any endemic infections  Throat culture—rules out streptococcal infection  CBC and ESR  Antistreptolysin O (ASO)/DNase titer at 2 weeks and 4 weeks interval  Stool examination.  Chest X-ray (CXR)— purified protein derivative (PPD) to rule out Koch’s, unilateral hilar lymph nodes—Infections and malignancy  CXR to rule out sarcoid—bilateral hilar lymph nodes  Biopsy the lesion to rule out vasculitis—Collagen vascular disease.
  • 19. DIFFERENTIAL DIAGNOSIS  Lupus panniculitis—present in fatty areas such as buttocks, posterior arms and leave scars  Tuberculous erythema induratum—usually ulcerate  Erythema nodosum leprosum  Acute urticaria—itching is intense  Nodular vasculitis-PAN—look for fixed livedo reticularis  Sarcoidosis  Superficial thrombophlebitis—linear tender streaks  Erysipelas  Filarial lymphadenitis  Insect bites.
  • 21. IBD
  • 22. APLA Lupus anticoagulant positive Anti Cardiolipin antibodies -positive
  • 23.
  • 24.
  • 25. CHRONIC ERYTHEMA NODOSUM  Chronic EN is a condition in which the lesions pop up elsewhere for a period of weeks to months  In most of the cases a cause is elusive  TB should be considered in our settings and a trial ATT may be given  Intense investigations to rule out sarcoid, IBD and collagen vascular disease (CVD) should be done  Rare association- Takayasu arteritis, vitamin B12 deficiency and Ehlers Danlos has been reported.
  • 27. THERAPEUTIC LADDER FOR EN  Discontinue possible causative medications  Treatment of underlying infectious diseases mainly streptococcal and TB  Bed rest and leg elevation and nonsteroidal anti- inflammatory drugs (NSAIDs) (aspirin, ibuprofen, indomethacin, naproxen)  Potassium iodide—saturated solution of potassium iodide-5–15 drops three times a day. Mechanism of action is exactly not known  Colchicine in the setting of Behçet’s disease
  • 28.  Various treatments for IBD like systemic steroids, HCQS, MMF, cyclosporine, thalidomide, infliximab and etanercept are effective in managing the underlying EN  Paradoxically both infliximab and etanercept have been reported to produce EN as a cutaneous side effect.  NSAID are to be avoided in IBD as they aggravate the disease  Systemic steroids - relatively safe therapeutic option if underlying infection, risk of bacterial dissemination or sepsis and malignancy has been excluded by a thorough evaluation  A general rule is 1 mg/kg (body weight)/day.
  • 29. USE OF POTASSIUM IODIDE  Saturated solution of potassium iodide 1,000 mg/mL  Droppers - for calibrations: 0.3 mL (300 mg),0.6 mL ( 600 mg)  In adults and older children, common dose = 300 mg TDS with starting dose = 150–300 mg TDS  Saturated solution of potassium iodide (SSKI)- bitter taste – water or fruit juice  Crystallization in cold - rewarming and shaking  Discard if solution turns yellow-brown Side effects: Acute—nausea, eructations, excessive salivation, urticaria, angioedema, small vessel vasculitis  Chronic—enlargement of salivary and lacrimal glands, acneiform eruptions, iododerma, hypothyroidism, hyperkalemia and occasionally hyperthyroidism
  • 30. PROGNOSIS  Erythema nodosum prognosis is excellent  The lesions resolve without any adverse reactions in most cases  Few cases are recurrent and refractory for which an underlying cause is to be ascertained and treated accordingly  Some of the idiopathic cases respond to colchicine/dapsone on prolonged treatment.
  • 31. CONCLUSIONS  Erythema nodosum is an acute panniculitis presenting as subcutaneous nodules most commonly due to infections and responds well to treatment  Chronic nodules need to be investigated thoroughly and treated accordingly.
  • 32. ACKNOWLEDGEMENTS  Dr Mala Saranathan ,Dermatologist  Dr G Srihari , Dermatologist  Dr M Srinivas , Pathologist  Dr M Santipriya , Pathologist