2. Necrobiosis= Nekros (death) + biosis (life): A condition of life and death.
Necrobiotic or collagenolytic or palisading granulomas are composed of altered
dermal tissue characterized by blurring and indistinct collagen bundles which
may sometimes be seprated with a decresed in connective tissue nuecli and
altered staining(eosinophilic or basophilic).
3. Conditions in which necrobiotic granulomas are seen
● Granuloma annulare(GA)
● Necrobiosis lipoidica (NL)
● Granuloma multiforme (GM)
● Necrobiotic xanthogranuloma (NXG)
● Rheumatoid nodules
● Reumatic fever nodules
● Palisaded neutrophilic and granulomatous dermatitis
● Other miscellaneous diseases
4. Granuloma annulare
-GA a chronic, non-infectious, granulomatous, necrobiotic disorder
primarily seen in children and young adults.
-Many studies report a female preponderance.
-Localized GA (75-80%) and generalized GA (10-15%) are the
commenest forms seen.
5. Etiology
Not clear but triggering factors are identified
Infections Drugs Immunization and others
HPV
Varicella virus
EBV
Parovirus
Scabies
Cat bite
Octopus bites
Allopurinol
Diclofenac
Quinidine
Amlodipine
TNF-alpha
inhibitor(commonest)
Insect bite
Bcg vaccination
Hept B vaccination
Sun exposure
PUVA therapy
Tuberculin skin test
Post waxing
6. Pathogenesis
● The pathogenetic mechanism that result in foci of altered connective tissue
surrounded by granulomatosis inflammatory infiltrate are not understood
• Various theories in the pathogenesis of GA
1. Post traumatic primary necrobiosis theory
2. Immune complex mediated vasculitis theory
3. Enzyme induced necrobiotic degeneration
4. Cell medicated delayed hypersensitivity
5. The role of immunological factors
6. Role of TNF-alpha, interferon-gamma, IL-2, matrix metalloproteinase
2 and 9
7.Primary collagen damage with increased synthesis of collagen that
may occur as a reparative process
7. 8. Elastic tissue injury with elastic fiber degeneration
9. In perforating GA- due to ischemic epidermal necrosis or transepithelial
elimination
It is thus believed that rather than a single mechanism in pathogenesis, multiple
mechanisms may interact with each other together and/or successively to induce
GA.
8. Clinical features
● The clinic features of GA depends on the variant occurring in the patient.
Coexistence of more than one clinical variant is seen.
9. Localized GA
● Most common variant(75-80%)
● Characterized Usually by asymptomatic non-scaly firm skin colored to
erythematous or violaceous papules which forms plaques in an annular or
arcuate pattern either by coalescing or remaining discrete.
● Hands and feet are the most common site
● Stretching the skin enables the papules to be seen more readily.
11. GENERALIZED GRANULOMA ANNULARE
● Associated with HLA-Bw35, late onset, [oorer prognosis and an altered lipid
profile.
● Characterized by skin colored hyper pigmented to violaceous and even
yellow colored papules coalescing to form plaques with raised margins.
● Pruritus is more common in generalized GA than in localized GA.
13. Disseminated granuloma annulare
● Characterized by extensive lesions of GA which are confined to the
extremities.
● Associated with DM, lymphoma( Hodgkin’s and non-Hodgkin’s), HIV
infection, hepatitis b and c infection, mycobacterium tuberculosis, cervical
adenocarcinoma, granulomatous mycosis fungoides, connective tissue
disease, EBV and TNF-alpha drugs( adalimumab, etsnercept).
15. Perforating GA
● Seen in 5% of all GA cases.
● Predominantly seen on hands and fingers as 1-4 mm umblicated papules,
covered with crusting or ulceration.
● This begins as erythematous to skin colored papules which become pustule
like lesions that eventually become umblicated.
● Scanty viscous or creamy discharge from crusts, and the lesion heals with
hypopigmentation, hyperpigmentation or atrophic scaring.
18. Subcutaneous
● Large , painless, skin colored nodules which May be mistaken for
rheumatoid nodules , leading to term psuedorheumatoid nodules
● It has a predilectation for children in the first 5-6 Years of life
● Typical locations include the palms, hands anterior tibial surfaces and feet
and rarely eyelids.
20. Histopathology
● GA is a granulomatus dermatitis characterised by focal degeneration of
collagen and elastic fibres museum deposition and a peri vascular interstitial
lymphohistocytic in filtrate in the upper and mid dermis
● The key to the histopathology diagnosis of GA is the identification of
hysteocytes in one of the three patterns
● Increase mucin is the hallmark of granuloma annualre
21. ● Most common is the infiltrative or interstitial pattern (about 70%)
● Scattered two sides are distributed between the collagen fibres, regeneration
of collage in fibres is minimum, but granular basophilic mucin deposition
between college and bundles can be highlighted with alcian blue and
colloidal iron stain
● Second pattern (25% of cases) is palisading
Consists of 12 several pelicating granulomas with Central connective tissue
degeneration surrounded by histiocytes sites and lymphocytes. Mucin is
abundant in the centre of pelicaded granulomas and fibrin, neutrophils and
nuclear dust maybe also present.
● Final Pattern is rare and it consist of epithelioid histiocytes nodules that can
resemble cutenous sarcoidosis
22.
23. Differential diagnosis
Annular type
● Consider
1. Tinea corporis
2. Subacute cutaneous lupus erythematosus
3. Neonatal lupus erythematosus
4. Actinic granuloma
● Rule out
1. Infections
2. Interstitial granulomatous dermatitis with arthritis
3. Lymphomas
Generalised type
● Consider
1. Lichen planus
2. Lichen nitidus
3. Molascum contagiousum
24. Rule out
1. Licheniod and granulomatous dermatitis of acquired immunodeficiency syndrome
2. Sarcoidosis
3. Lymphoma
Subcutaneous type
● Consider
1. Erythema nodusum
2. Dermoid cyst
3. Rheumatic nodules
● Rule out
1. Epithelioid sarcoma
2. Benign or other malignant tumors
3. Deep infections
25. Perforating type
● Consider
1. Mollascum contagiousum
2. Insect bites
3. Pityris licheniod
4. Perforating collagenosis and other perforating disorders
5. Foreign body granuloma
Patch type
● Consider
1. Morphea
2. Erythema annulare centrifugum
3. Parapsoriasis
● Rule out
1. Lymphoma
26. Treatment Options for granuloma annulare
● Localized GA is genrally a benign and self limiting disease with
spontaneous resolution occurring in 40-50% of the patients within 2 years.
● Reverse koebner phenomenon occurs in GA with the lesion disapperring
after skin biopsy.
● Localized GA- Corticosteroid (Topical steroids with or without
occulusion/interalesional), calcineurin inhibitors(0.1% tacrolimus/
1%pimecrolimus), 5% imiquimod, cryotherapy, co2 laser therapy,
intralesional interferon gamma, photodynamic therapy with 5-aminolevulinic
acid, pulsed dye laser, electrodessication, 5- flurouracil.
27. ● Generalized and disseminated GA-
Psoralen plus UVA(PUVA) therapy
Dapsone(100mg/day) and isotretinoin (0.5-0.75 mg/kg/day)
PUVASOL(Psoralem followed by sunlight exposure)
Oral calcitriol, methotrexate,
28. Necrobiosis lipoidica
● Raised by sharply demarcated place of atrophic yellow skin which may
ulcerate.
● Female To male ratio is 3:1
● Young and early middle age is affected
● Necrobiosis lipoidica and diabetes mellitus- In a study 11% of cases of NL
head DM by in similar percentage of patient glucose intolerance is found
29. Pathogenesis
● 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 college in scene in NLD and this both his is supported by the
presence of immuno reactant deposited in the vessel wall of legional as well as
uninvolved skin in patients with NLD, and this hypothesis is supported by the
presence of immuno reactant deposited in the vessel walls of lessional as well as
uninvolve skin in patient with NLD
● It is also postulated that the microangiopathic vessels changes seen in diabetic patient
could contribute to development of collagen degeneration and subsequent dermal
inflammation
30.
31. Clinical features
● NLD presence clinically with yellow brown atrophic , talengiectatic plaques rounded
by raised violacious rims typically in free tbl region having GLAZED PORCELAIN
appearance
● Start as small, Red brown pebules that gradually and largest and then develop Central
epidermal atrophy. Lessons are multiple and occur with bilateral symmetry
● Ulceration occurs in 35% of lesions usually following minor trouma
● Less typically an automatical location for NLD include the upper extremities face
where the lesions may be more angular or serpyginious in configuration and are less
atrophic
32.
33.
34. Histopathologically
● The epidermis is normal or atrophic and absent if there is ulceration .
Changes includes its full thickness and often extent into subcutaneous fat. Early lessons
show a perivascular and interstitial mixed inflammatory cell in filtrate.
● Areas of necrobiosis are usually more extensive and less well defined.
● There is degeneration of collagen and elastin within lesions.
● Histiocytes borders the area of necrobiosis. There are variable number of.
langarhance or foreign body giant cell.
● Small, superficial blood vessels are increased in number and telangiectatit.
35.
36. Associated condition
● Other than diabetes mellitus (in 75% of patients) and GA (which is
sometimes seen) rheumatologic, endocrino and hematologic disorders are
known to occur in association with necrobiosis lipoidica.
● Infections and inflammatory board diseases a n c a positive vasulitis
syndrome sarkoirosis are sporadically reported associations. Microbiosis
lipoidica in patient with systemic diseases present a typical clinical features
with respect to location, morphology or both
37. Treatment
● First line therapy include potent topical corticosteroid for early lesions and
intralesional corticosteroids injected into the active border of established
lesion
● Other Therapeutic modalities include
1. Puva therapy
2. Topical tacrolimus
3. Fumaric acid esters
4. Thalidomide
5. Chloroquine
6. Clofazimine
7. PGE1
38. Granuloma multiforme
● Chronic granulomatus skin condition characterised clinically by firm papules
aggregated into plaques or forming the edges of annular lesions and
histologically by focal necrobiosis and hysteocytic granulomas
● The primary event may be sun induced damage to dermal connective tissue.
39. ● The upper, uncovered part of body are predominantly affected
● The initial lesions are small flesh coloured pepules which become aggregated
into plakes or form the elevated rims of annular lesion
● In The Larger annular lesions the central area is often hypopigmented
● Pruritis may be prominent
● The condition last for months or year, and may persist indefinitely.
40. Pathology
● Histologically the relations show necrobiosis in the dermis with the history of
cytic granuloma as an other necrobiotic disorder.
● Multi nucleated giant cells are prominent. Phagocytosis of elastic tissue has
been present.
41. Differential diagnosis
-Clinically granuloma multiform mein has to be differentiated from
tuberculoid leprosy by the absence of sensory changes in the patch. Histologically
the absence of nerve infiltration is distinguishing feature.
-Peenya sarcinata can be ruled out by the absence of itching. In case of doubt
scraping for fungus should be taken from the periphery.
figurate erythema, where the individual relations may closely resemble
granuloma multiform is less persistent. Histologic differentiation is also possible
since the characteristic microbiosis and granuloma are absent.
-circinate syphilide can be ruled out by serological test for syphilis.
42. Treatment
● Topical and intralesional corticosteroid are hardly effective.
● Dexamethasone- cyclophosphamide pulse therapy
● Low dose melphalan, chlorambucil, cyclophosmphamide and
plasmapheresis.
