Necrobiotic disorders

1. TUTORIAL PRESENTATION
NECROBIOTIC DISORDERS

2. GRANULOMA ANNULARE
Calcott Fox first described ‘ringed eruption of the
fingers’ in 1895.
 Radcliffe-Crocker called this as granuloma annulare
in 1902
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It occurs in all age groups but is rare in infancy
 Many studies report a female preponderance
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3. ETIOLOGY
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Etiology is not clearly understood but triggering
factors are identified
INFECTIONS
HPV
VARICELLA VIRUS
EPSTEIN–BARR
VIRUS (EBV)
HIV
PARVOVIRUS B19
HEPATITIS C VIRUS
BORRELIA
BURGDORFERI
SCABIES
DRUGS
Immunization &
Other
Allopurinol,
Diclofenac,
Quinidine
calcitonin,
Amlodipine
Insect bite
a cat bite waxinginduced
pseudofolliculitisT
uberculin tests
BCG vaccination
Hepatitis B
vaccination
HLA-Bw35
Sun exppsure
PUVA Therapy

4. PATHOGENESIS
The pathogenetic mechanisms that result in foci of
altered connective tissue surrounded by a
granulomatous inflammatory infiltrate are not
understood
 Proposed mechanisms include

a primary degenerative process of connective tissue
initiating granulomatous inflammation,'s
 lymphocyte-mediated immune reaction resulting in
macrophage activation and cytokine mediated
degradation of connective tissue
 a subtle vasculitis or other microangiopathy leading to
tissue injury


5. CLINICAL FEATURES
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Benign, usually self-limited cutaneous disease that classically
presents as arciform to annular plaques located on the
extremities of young people (J Am Acad Dermatol)
The approximate distribution of GA lesions is
(Pediatr
Dermatol )
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60% isolated to the hands and arms,
20% on the legs and feet,
7% on both upper and lower extremities,
5% on the trunk
5% on the trunk plus other areas.
The plaques may be skin-colored, pink or violaceous in
color, and, upon close inspection, are found to be composed
of individual small papules measuring a few millimeters in
diameter
Stretching the skin enables the papules to be seen more
readily.
The surface of the skin over the papules is intact and there is
usually no scaling

6. CLINICAL VARIANTS
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(FITZPATRICK)
Localized
Generalized,
Subcutaneous
Perforating, and Patch types
Linear granuloma annulare
Follicular pustular form
Papular umbilicated lesions in children
There is overlap between the different variants, and
more than one morphologic type may co-exist

7. LOCALIZED
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The most common form
Usually presents as annular
or arcuate lesion
It may be skin colored
erythemarous or violaceous
Usually 1 to 5 cm in
diameter
The annular margin is firm
to palpation and may be
continuous or consist of
discrete or coalescent
papules in a complete or
partial circle

8. GENERALIZED

Can occur upto 15% of patients

characterized by myriad small
skin-colored to pink-violet
papules in a symmetric
distribution on the trunk and
extremities.
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Some of these papules may
coalesce to form small annular
plaques .
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Generalized GA
 later age of onset,
 poorer response to therapy
 an increased prevalence of
the HLA-Bw35 allele
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In one study of 100 patients
with generalized GA, 45% had
lipid abnormalities, including
hypercholesterolemia, hypertrigl
yceridemia, or both

9. PERFORATING
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Characterized by
trasepidermal
elimination of
necrobiotic collagen
Superficial papules with
central umbilication or
crusting with discharge
of creamy fluid
Lesion heal with
atrophic or
hyperpigmented scars.
Can develop over
zoster scars and tattos

10. SUBCUTANEOUS
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Large, painless, skin-colored
nodules which may be
mistaken for rheumatoid
nodules, leading to the term
pseudorheumatoid nodule.
It has a predilection for
children in the first 5 to 6 years
of life.
Typical locations include the
palms, hands, anterior tibial
surfaces and feet, as well as
the buttocks, scalp
and, rarely, the eyelids.
As many as 50% of patients
with deep GA lesions also
have associated classic
lesions.

11. DISAESE ASSOCIATION
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GA has been described as a paraneoplastic granulomatous
reaction to solid organ tumors, Hodgkin disease, non-Hodgkin
lymphoma and granulomatous mycosis fungoides In these
patients, the clinical pattern is frequently atypical, with painful
lesions in unusual locations, including the palms and soles.
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Many reports supporting or refuting the association of GA with
diabetes mellitus have been published.
In a retrospective study of 84 patients, 12% were found to
have diabetes mellitus, and these patients were more likely to
suffer from chronic relapsing GA than were non-diabetic
patients (Dermatology 1996)
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Classic GA and perforating GA may occur in herpes zoster
scars
Atypical variants of GA have been associated with HIV
infection

12. HISTOPATHOLOGICALLY
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GA is a granulomatous dermatitis characterized by focal
degeneration of collagen and elastic fibers, mucin
deposition, and a perivascular and interstitial lymphohistiocytic
infiltrate in the upper and mid dermis.
The key to the histopathologic diagnosis of GA is the
identification of histiocytes in one of three patterns.
Increased mucin is the hallmark of granuloma annulare

13. 
The most common is the infiltrative or interstitial
pattern(about70%)
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The second pattern (25% of cases) is palisading
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scattered histiocytes are distributed between collagen fibers.
Degeneration of collagen fibers is minimal, but granular, basophilic
mucin deposition between collagen bundles can be highlighted with
Alcian blue and colloidal iron stains
It consists of one to several palisading granulomas with central
connective tissue degeneration surrounded by histiocytes and
lymphocytes . Mucin is abundant in the center of the palisaded
granuloma, and fibrin, neutrophils and nuclear dust may also be
present.
The final pattern is rare, and it consists of epithelioid
histiocytic nodules that can resemble cutaneous sarcoidosis

15. DIFFERENTIAL DIAGNOSIS

17. TREATMENT

18. NECROBIOSIS LIPOIDICA
Necrobiosis lipoidica was first described by
Oppenheim, in 1930
 Named by necrobiosis lipoidica diabeticorum by
Urbach, in 1932.
 Characterized by sharply demarcated plaques of
atrophic yellowish skin, which may ulcerate.
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19. EPIDEMILOGY
Female to male ratio is 3:1
 Young and early middle age is affected
 Necrobiosis lipoidica and diabetes mellitus
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In a study 11 percent of cases of NL had DM while in
similar percentage of patients glucose intolerance is
found.
 No relation with degree of hyperglycemia and likelihood
of NL is found
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20. PATHOGENESIS
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The etiology and pathogenesis is not known but
some hypothesis are present
Immunologically mediated vascular disease has been
suggested as the primary cause of the altered collagen
seen in NLD, and this hypothesis is supported by the
presence of immunoreactants deposited in vessel walls
of lesional as well as uninvolved skin in patients with
NLD.(Arch Dermatol )
 It is also postulated that the microangiopathic vessel
changes seen in diabetic patients could contribute to the
development of collagen degeneration and subsequent
dermal inflammation
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21. CLINICAL FEATURES
NLD presents clinically with yellow–brown, atrophic,
telangiectatic plaques surrounded by raised,
violaceous rims, typically in the pretibial region
having GLAZED-PORECLAIN appearance.
 The lesions start as small, firm, red–brown papules
that gradually enlarge and then develop central
epidermal atrophy. Lesions are often multiple and
occur with bilateral symmetry.
 Ulceration occurs in 35% of lesions usually
following minor trauma.
 Less typical anatomic locations for NLD include the
upper extremities, face and scalp, where the
lesions may be more annular or serpiginous in
configuration and are less atrophic
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24. HISTOAPTHOLOGICALLY
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The epidermis is normal or atrophic, and absent if there
is ulceration.
The dermal changes involve its full thickness, and often
extend into the subcutaneous fat. Early lesions show a
perivascular and interstitial mixed inflammatory cell
infiltrate.
Areas of necrobiosis are usually more extensive and
less well-defined.
There is degeneration of collagen and elastin within
lesions .
Histiocytes border the areas of necrobiosis. There are
variable numbers of Langhans’ or foreign-body giant
cells.
Small, superficial blood vessels are increased in number
and telangiectatic

26. TREATMENT
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First-line therapy includes potent topical corticosteroids
for early lesions and intralesional corticosteroids injected
into the active borders of established lesions.
Other therapeutic modalities include:
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PUVA therapy
Topical tacrolimus
Fumaric acid esterst
Thalidomide
Chloroquine
Highdose nicotinamide
Clofazimine
Pentoxifylline
Tretinoin (0.05%)
Prostaglandin E1

27. GRANULOMA MULTIFORME
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A chronic granulomatous skin condition,
characterized clinically by firm papules aggregated
into plaques or forming the edges of annular
lesions, and histologically by focal necrobiosis and
histiocytic granulomas
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The primary event may be sun-induced damage to
dermal connective tissue

28. The upper, uncovered parts of the body are
predominantly affected.
 The initial lesions are small, flesh-coloured papules
which become aggregated into plaques or form the
elevated rims of annular lesions.
 In larger annular lesions the central area is often
hypopigmented.
 Pruritus may be prominent
 The condition lasts for many months or years, and
may persist indefinitely.
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