A lecture presented by Dr/ Rania Alakad (dermatologist, Egypt) at EADV congress 2018 about atypical presentations of erythema nodosum leprosum

1. Atypical presentations of erythema
nodosum leprosum:
A diagnostic and therapeutic challenge
Rania Alakad, M.D
Lecturer, Dermatology & Venereology Department
Zagazig University, Egypt
raniaelaqad@zu.edu.eg

2. No conflict of interest

4. • lesions progressed
in the last 2 to 3 w
in association with
fever &joint pain.

5. Ex: red tender
plaques with
vesicles and
pseudo-vesicles
in an annular
pattern on her
abdomen.

8. Sweet’s
syndrome

9. Grenz zone
Vacuolated
histiocytes
(virchow’s cells)

10. Extensive neutrophilic
infiltrate

11. Vasculitis +

12. S100+ nerve
fibers
surrounded by
granulomatous
infiltrate

13. • Painful erythematous plaques.
• Pseudo-vesicular lesions.
• Dermal infiltrate of foamy histiocytes.
• Extensive neutrophilic infiltrate.
• Vasculitis.
• Positive slit-skin smear for lepra
bacilli 4+.
Borderline lepromatous leprosy
Sweet’s Syndrome-like
erythema nodosum leprosum

14. • Atypical presentations of erythema nodosum leprosum.
• 20 – 30 newly diagnosed leprosy patients in our clinic /
year.
• 2 out of 10 leprosy patients may develop lepra reaction.

15. Erythema nodosum leprosum ENL
(Ramesh et al, 2010)
• During the course of MDT therapy.
• After discontinuation of therapy.
• The initial presentation of leprosy.

16. Typical ENL
• Acute eruption of tender,
erythematous evanescent
papules, plaques or nodules
usually between existing
lepromatous lesions.
• The face and extremities are the
most frequent sites in a bilateral
and symmetrical pattern.
(Yogeesh et al, 2012). (Kahawita & Locwood , 2008)

17. • Therefore, ENL is considered
atypical when present with any
form other than the classic tender,
erythematous plaques and nodules
associated with constitutional
manifestations ± lepromatous lesions.
Atypical ENL

19. Methods
To facilitate identification of this treatable yet potentially life-
threatening condition
• Clinical
• Histologic
• Therapeutic aspects
100 cases of atypical ENL.
Those cases were reported earlier in the medical literature in addition
to the new case presented to our clinic.

20. • A systematic review of medical literature was done
for all case reports of atypical presentations of ENL in
PubMed database until 2018.
• the following search terms: atypical, erythema
nodosum leprosum, bullous, pustular, ulcerative,
necrotic, erythema multiforme, sweet syndrome and
erythema necoticans.
Methods

21. Categories of previous cases of atypical ENL according to the
prevalence of the main 5 clinical patterns:
Methods
 Vesiculo/bullous pattern including all the blistering forms.
 Ulcero /necrotic pattern.
 Pustular pattern.
 Targetoid pattern (all patients presenting as typical targets).
 Sweet’s syndrome-like pattern ( typical edematous
plaques with pseudo-vesicles).

22. 46%
13%
28%
10%
3%
Vesiculo-bullous
Targetoid
Sweet’s
syndrome like
Ulcero-necrotic
Pustular
Results

23. 1
• Vesiculo-bullous ENL
2
• Ulcero-necrotic ENL
3
• Pustular ENL
4
• Sweet’s syndrome like ENL
5
• Targetoid ENL

24. Vesiculo-bullous ENL
Clinically:
• The blisters can be flaccid /
tense / hemorrhagic.
Histologically:
• Intra / subepidermal bullae.
• Epidermal spongiosis and
acantholytic cells.
(Bakshi et al., 2017)

25. Ulcero-necrotic ENL
Clinically:
• Deep painful ulcers and necrotic
skin lesions.
Histologically:
• Acute necrotizing vasculitis is
present to a greater degree in the
ulcero-necrotic variants with
heavier inflammatory infiltrate.
(Yogeesh et al., 2012)
(Dillon et al., 2015).

26. Histologic data
• Leukocytoclastic vasculitis
is a major pathological
event in type II reactions.
However, not all ENL skin
biopsies show evidence of
vasculitis
(polycarpou et al., 2017).

27. Ulcer-necrotic lesions
1. Lazarine leprosy.
2. Lucio’s phenomenon(type3 lepra
reaction).
3. Neuropathic ulcer.
4. Antiphospholipid syndrome in a case
of leprosy.

28. Ulcero-necrotic ENL
1. Good response to
thalidomide.
2. Fever, constitutional
symptoms, visceral
involvement, and neuritis.
3. Acute necrotizing
vasculitis.
Lucio’s phenomenon
1. No response to
thalidomide.
2. No fever/ constitutional
symptoms or visceral
involvement.
3. Vascular thrombosis,
ischemic necrosis.

29. Pustular ENL
• In pustular forms, certain
triggers can induce the release
of cytokines which damage
the normal dermal structures
with the influx of neutrophils.
(kuo et al, 2017) (Ramesh et al, 2010)

30. Pustular ENL
• Higher expression of E-selectin on the vascular walls in
ENL promotes neutrophil migration and adhesion
to endothelial cells.
Intraepidermal neutrophilic pustules are
responsible for the clinical pustules in pustular ENL.

31. Sweet’s syndrome – like ENL
• Intense dermal edema in ENL can
lead to pseudo-vesicular pattern
which gives resemblance to
Sweet’s syndrome.
• With the evolution of the lesions,
there may be a central clearing,
resulting in target aspect similar to
EM.
(Chiaratti et al, 2016).

32. • In the case of sweet’s
syndrome-like ENL, extensive
infiltration of neutrophils
occurs in the papillary dermis
with pronounced edema
which mimics the pathology
of Sweet’s syndrome lesions
itself.
Sweet’s syndrome – like ENL
(Chiaratti et al, 2016).

33. (Mishra et al., 2015)

34. Histologic data
100 100
14
25 28
0
20
40
60
80
100
120
vacuolated histiocytes neutrophilic infiltrate
vasculitis dermal edema
intra/subepidermal bullae

35. Extra-cutaneous manifestations
0
20
40
60
80
100
120
fever arthralgia acral edema
lymphadenopathy iridocyclitis neuritis
epididymorchitis

36. Bacteriological index (BI)
In the studied cases of atypical ENL
Smears taken from the skin lesions
The chief attributing risk factor of ENL is a high
bacteriological index (BI) > +4.
The severity of lesions is related to the size of bacterial
load.
BI: + 2 to + 6
a mean of + 4

37. A significantly higher risk
Multiple ENL
Monitoring throughout MDT therapy
Patients:
1. Younger < 40 years old.
2. Lepromatous leprosy disease.
3. A mean BI of >4+.
(Manandhar et al, 1999)

38. ENL is more common when:
The morphological index (MI) <5
i.e., when there is a large number of dead bacilli
 Abrupt release of large number of killed bacilli is
responsible for the activation of immune system.
 This explains the high incidence of leprosy reactions
shortly after MDT.
(Manandhar et al., 1999)

39. Viable bacilli with intact cell wall can evade or suppress the
immune system through escaping NK cell-mediated killing in
macrophages and Schwann cells.
Killed and fragmented bacilli are well recognized by the
immune system. The fractionated cell membrane can induce
IFN-γ in CD4+ and CD8+ T cells .
(Degang et al., 2014)

40. Treatment
The treatment regimen of cases of atypical
ENL was similar to that of typical case.
• Continuation of MDT
• systemic steroids were the main line of therapy in
all reported cases
• Thalidomide was given in 21% of patients.
• Drugs with ant-inflammatory properties e.g.
colchicine, dapsone, NSAIDS and minocycline have
also been tried.

41. Thalidomide has been chosen as the treatment
of choice mainly due to its speed of action (effective
in 24 h in most cases) as well as its ability to spare the
prolonged use of steroids.
• Still the use of thalidomide is limited by its side
effects including teratogenicity, neuropathy
(Meyerson et al, 1996).

42. 1- A skin eruption of acute onset accompanied by
fever and bad general condition.
2- Systemic complaints e.g. bone and joint pain,
neuritis, red eye and lymphadenopathy.
3- Prolonged contact with a lepromatous relative.
Recommendations
The dermatologist should pay attention to the following signs
when suspect a case of Atypical ENL:

43. Recommendations
4- Existing lesions of typical leprosy and typical
ENL are usually present as well as other signs such as
madarosis, leonine face and icthyosis.
5- The pathological findings and identification of
lepra bacilli.
The dermatologist should pay attention to the following signs
when suspect a case of Atypical ENL :

44. Conclusions
The diagnosis of atypical forms of ENL in already
known "leprosy" patients is an easier task.
Leprosy presenting for the 1st time with atypical
ENL represents a diagnostic dilemma that can
lead to delayed diagnosis and treatment.
Clinicians and pathologists should be familiar
with these unusual presentations.

45. Acknowledgements
 Dr/ Ahmad Nofal
MD
Professor
Dermatology & Venereology
department
Zagazig University, Egypt
 Dr/ Magda Assaf
MD, PhD
Professor
Pathology Department
Zagazig University, Egypt

46. Thank you