Panniculiits Dermatology

1. Panniculitis:
Dr.Asmat
Resident Dermatology
Ref: Rook’s Dermatology

2. Superficial Migratory Thrombophlebitis
▪ Inflammation and thrombosis of the superficial veins
▪ Painful induration with erythema
▪ Oftenly linear or branching configuration forming cords
1

3. Predisposing agents:
 Primary hypercoagulable states
 Antiphospholipid syndrome
 Deficiencies of
• Protein C
• Protein S
• Heparin co‐factor II
• Antithrombin III
• Factor XII
•Tissue plasminogen activator
• FactorV Leiden

4. Predisposing agents:
Secondary hypercoagulable states
•Trousseau syndrome (Paraneoplastic)
• Behcet syndrome
• Buerger disease
• Pregnancy
• HIV‐associated immune reconstitution syndrome (IRIS)
• Secondary syphilis
• Infectious suppurative thrombophlebitis
(S.aureus, E.coli, P.aeruginosa or fungi)
• Oral contraceptive pills
• Sepsis, IV injections or catheterizations

5. Histopathology:
▪ Luminal thrombosis and an inflammatory infiltrate in vein wall of fat lobule
▪ Early infiltrate (Neutrophils)
▪ Granulomatous infiltration participates in the recanalization of the thrombus
▪ Vein damage does not extend to djacent fat lobule

6. b)Thrombosis in the lumen of
the involved vein
a) large vein in the septa of subcutaneous tissue
ivolved

7. Clinical Featrues:
▪ Pain and swelling at the affected area eg. Leg, ankle
▪ Slight colour change (red to blue) and tenderness along a part of the affected vein
▪ Thickened and firm nodules and plaques

8. Differential Diagnosis:
o Superficial Migratory thrombophlebitis
i. Large veins of the septa in upper subcut.Tissue
ii. Damaged vessel is a vein with little or no discernible internal elastic membrane
o Cutaneous Polyarteritis nodosa
i. Small artries and arteriols in subcutaneous septa
ii. Sharp and prominent internal elastic membrance on ELASTIC stain

9. Differential Diagnosis:
o Tuberculid, nodular granulomatous phlebitis
i. Tuberculoid granulomas and multinucleate giant cells

10. Cutaneous Polyarteritis Nodosa
▪ Cutaneous vasculitis affecting subcutaneous arteries and arterioles
▪ Circulating p‐ANCA antibodies with peripheral staining
▪ Little or no evidence of systemic disease
2

11. Pathophysiology:
▪ The serum Circulating p‐ANCA antibodies with peripheral staining
(negative for p‐ANCA by ELISA)
▪ Serum anti‐LAMP‐2 levels elevated
▪ Anti‐PS/PT IgG antiphosphatidyl serine– prothrombin complex antibodies
& IgG anticardiolipin antibodies

12. Histophathology:
▪ vasculitis involving medium‐sized arteries and arterioles at the
septa of the upper subcutis
▪ vessel appears with a thickened wall, within which an inflammatory
infiltrate

13. Histophathology:
▪ early lesions  a neutrophilic infiltrate and leukocytoclasis, the
intima of the involved artery exhibits an eosinophilic ring of
fibrinoid necrosis, givinga target‐like appearance to the damaged
vessel
▪ older lesions  lymphocytes , entire thickness vessel wall fibrosis
leads to the obliteration of its lumen.

14. Histophathology:
▪ Little or no involvement of the adjacent fat lobule septal arteritis.
a) vessel of the septa of subcutaneous fat b) fibrinoid necrosis of the arteriole intima
(target‐like appearance)

15. Necrobiosis lipoidica
▪ Shiny, red‐brown or yellowish plaques in the skin (shins )ulcerate
sometimes
▪ Associated with diabetes & Subcutis involvment
▪ Degenerated dermal collagen is surrounded by a granulomatous
inflammatory respons
3

16. Histopathology:
▪ lesions full thickness of the dermis superficial subcutaneous tissue
(septal panniculitis)
▪ palisading granulomas with histiocytes surrounding areas of
degenerate collagen within widened septa
▪ Alternating horizontal bands of inflammatory cells and fibrosis (entire
dermis)

17. Histopathology:
▪ Early lesions : inflammatory infiltrate neutrophils scattered within the
septa
▪ Later lesions: histiocytes, lymphocytes & plasma cells with lymphoid
follicle
▪ Multinucleated giant cells involving the septa resemble erythema
nodosum

18. Histopathology:
a) full thickness of the dermis & extension to
the subcutaneous tissue throughout the septa
b) Granulomas involving the thickened
fibrous septa of the subcutaneous tissue

19. Differential diagnosis :
▪ Morphea
In NBL the dermis and the superficial subcutaneous tissue are replaced by horizontal
fibrosis with sclerotic collagen bundles
▪ Erythema Nodosum
only other than a perivascular lymphocytic infiltrate

20. Pathogenesis of NBL in Diabetes
▪ GLUT‐1 immunohistochemical expression
▪ sclerotic collagen of necrobiosis lipoidica
▪ disturbance in glucose transport by fibroblast
▪ histogenesis of necrobiosis lipoidica

21. Morphea:
▪ A group of related diseases of poorly understood aetiology affecting
principally skin and subcutaneous tissue and characterized by
variable fibrosis, sclerosis and cutaneous atrophy
4
Morphoea profunda.The lesions
consisted of indurated,
hyperpigmented and slightly
depressed plaques.

22. Pathophysiology:
▪ morphoea profunda
▪ Eosinophilic fasciitis
▪ disabling pansclerotic morphoea of children

23. Pathophysiology:
▪ Classical morphoea extends from the deep dermis to the
subcutaneous tissue
▪ Morphoea here is panniculitic process with no involvement of the
epidermis, cutaneous adnexa or dermis.The process is known
variously as morphoea profunda, nodular scleroderma or keloidal
scleroderma

24. Histopathology:
▪ marked fibrous thickening of the septa of subcutaneous fat
▪ Collegen replacing fat around the eccrine coils
▪ homogeneously eosinophilia due to sclerotic process involving both
dermis and subcutis

25. Histopathology:
▪ Inflammatory infiltrate of Lymphocytes surrounded by plasma cells at
the interface between the thickened septa and the fat lobules.
▪ Eosinophilic fasciitis (Shulman syndrome) is regarded as a variant of
deep morphoea with similar histpath features

26. Histopath:
a) sclerosis of the deeper reticular dermis
and the septa of subcutaneous tissue
b)Thickened sclerotic collagen bundles
with interstitial lymphocytes and plasma cells

27. Subcutaneous granuloma annulare:
▪ Rare clinicopathological variant of granuloma annulare
▪ Subcutaneous nodules that may appear +/- classical dermal papular
lesions
5
Subcutaneous granuloma
annulare involving the lateral
aspect of the
first phalanx of the third right
finger in a 14‐year‐old boy

28. Pathophysiology:
▪ An immunoglobulin‐mediated vasculitis causes necrobiotic areas in
granuloma annulare
▪ Cell‐mediated immune response
(T cells and CD1a‐positive Langerhans cells, aTh1 inflammatory reaction)
eliciting matrix & elastic tissue Degradation ---
collagen synthesis

29. Differential Diagnosis:
o Subcut Granuloma Annulare
▪ central necrobiotic areas exhibit pale and mucinous centre with
basophilic tendency
o rheumatoid nodule
 necrobiotic centre exhibit homogeneous and eosinophilic with
abundant fibrin
old lesion shows extensive fibrosis in centre

30. Differential Diagnosis:
o necrobiosis lipoidica
▪ full thickness of the dermis and the subcutaneous involvement is
just a deep extension from the dermis into the connective tissue
septa of the subcutis
o epithelioid sarcoma
▪ neoplastic process central areas of degenerate collagen
epithelioid cells + hyperchromatic and pleomorphic nuclei + mitotic
figures
▪ Neoplastic cells CD-34 +ive (immunehistochemistry)

31. Histopathology:
a) involvement of deeper dermis and
subcutaneous tissue
b) several areas of degenerate collagen bundles
surrounded by a palisade of histiocytes
 basophilic degeneration of collagen bundles with peripheral palisading
granulomas involving the connective tissue septa of the subcutis
 CD68/PGM1 in the histiocytic population and a variable one of lysozyme (IHC)

32. Subcutaneous granuloma annulare:
▪ extra‐articular manifestations of rheumatoid arthritis
▪ found in proximity to joints or extensor surfaces
6
Rheumatoid nodules involving
the dorsum of the fingers in an
adult
woman with seropositive
rheumatoid arthritis

33. Pathophysiology:
▪ The pahtogenesis is unknown exactly , there are some hypothesis
and obeservations
▪ immune complex mediated IgG and IgM by DIF in the vessel walls of
rheumatoid nodules, suggests vasculitic process

34. Pathophysiology:
▪ microchimerism demonstrated in 50% of the cases of rheumatoid
nodules of patients with RA
▪ the formation of rheumatoid nodules is driven byTh1 lymphocytes
(cytokine profile identified IFN‐γ,IL‐2, IL‐1β,TNF‐α , IL‐12, IL‐18, IL‐15 and IL‐10)

35. Variant:
▪ Accelerated rheumatoid nodulosis (ARN) :
The development of new painful rheumatoid nodules in patients with chronic
RA under treatment of methotrexate.

36. Rheumatoid Nodule Subcutaneous GA Necrobiosis Lipoidica
Location Subcutaneous septa Subcut septa+ upper+mid
Reti dermis
Full thickness dermis + subcut
Pattern Degenerate collagen +fibrin
deposition(eosinophilic gran)
degenerate collagen
+(basophilic necrobiotic gran)
Fibrosis +ill‐defined collagen
degen area (eosinophilic
necrobiotic gran)
Collegen Degeneration Complete Complete Indistinct, elongated
degenerate collagen areas
Fibrosis Common unommon Common
Histocytosis Well‐defined palisades of
histiocytes
Well‐defined palisades of
histiocytes
nterstitial histiocytes, no
palisading
Differential Diagnosis:

37. Rheumatoid Nodule Subcutaneous GA Necrobiosis Lipoidica
Inflammtory
Components
Tuberculoid and sarcoid
reaction common
Tuberculoid and sarcoid
reaction uncommon
Tuberculoid and sarcoid
reaction common
Vascular Anomaly Capillary hyperplasia at the
periphery
Perivascular lymphocytes Capillary wall thickening
Mucin Variable Common Variable
Fibrin Common No Variable
Differential Diagnosis:

38. Histopathology:
▪ Early Lesion: Granulation tissue surrounded by mononuclear cells
and fibroblasts
▪ Later stages: Central area of degenerate collagen with fibrinoid
material & surrounded by a palisade of elongated mononuclear
histiocytes

39. Histopathology:
▪ Central degenerated zone : Eosinophilic amorphous, granular or
fibrillary material containing collagen fibrils, fibrin and cellular
debris
▪ Peripheral zone: Multinucleated giant cells,T lymphocytes, plasma
cells, mast cells and eosinophils

40. Longstanding rheumatoid nodules exhibit extensive fibrosis in which clefts
and cystic degeneration appear due to liquefactive degneration
a) replacement of subcutaneous tissue by a fibrotic
process with scatteredareas of degenerate collage
b) he eosinophilic fibrinoid areas are
surrounded by a palisade of histiocytes

41. Necrobiotic xanthogranuloma:
▪ a rare histiocytic disorder with progressive destruction of the
involved cutaneous & extracutaneous tissues
▪ Multiple indurated yellow‐red or violaceous plaques or nodules,
involving periorbital skin.
7

42. Pathophysiology:
▪ Monoclonal paraprotein binds to monocyte lipoprotein receptors to
form xanthomata
▪ immune complexes inducing granuloma formation
▪ central areas of necrobiosis in lesions of necrobiotic
xanthogranuloma is as result of ischaemia

43. Differential Diagnosis:
▪ Necrobiosis lipoidica:
extend to subcutaneous tissue
▪ Subcutaneous granulomaAnnulare:
occurs mainly in children and does not tend to ulcerate
▪ Juvenile xanthogranuloma :
large areas of degenerate collagen (as in NXG) are not seen
▪ Deep xanthomas:
large areas of degenerate collagen (as in NXG) are not seen

44. Histopathology:
▪ Foamy histiocytes & someTouton‐like multinucleated giant cells in dermis
▪ From the dermis, infiltrate extends to connective tissue septa of subcutis
▪ degenerate collagen bundles and cholesterol clefts within the diffuse infiltrate

45. Histopathology:
▪ palisading granuloma of epithelioid histiocytes is present around the areas
▪ IHC +ive for lysozyme, CD68, Mac387 & CD11b on histiocytes + foamy
macrophages

46. a) diffuse involvement of the entire
thickness of the dermis and
extension to subcutaneous tissue
b) Areas of degenerate collagen with
abundant cholesterol clefts.

47. Erythema nodosum:
▪ A cutaneous reaction process with sudden eruption of several
erythematous, tender, non‐ulcerating nodules & plaques, typically
located on the shins
▪ It is triggered by a wide variety of infectious , inflammatory
disorders, malignant neoplasms & medications
▪ The most common triggers are bacterial
infections, sarcoidosis & IBD
8

48. Common causes:
▪ Infections : β‐haemolytic Streptococcus, tuberculosis
▪ Drugs :sulfonamides, bromides andoral contraceptive pills

49. Associated Diseases:
▪ Sweet syndrome
▪ erythema nodosum
▪ sarcoidosis
▪ throat infection
▪ acute myelogenous leukaemia
▪ Crohn disease

50. History:
▪ fever of 38–39°C, fatigue, malaise, arthralgia, headache, abdominal
pain, vomiting, cough or diarrhoea
▪ Episcleral lesions & phlyctenular conjunctivitis accompany
cutaneous lesions

51. Presentation:
▪ Sudden onset of symmetrical, bilateral, tender, erythematous, warm nodules &
raised plaques ivolving shins, ankles & knees
 Early lesions show a bright red colour and are raised slightly above the skin
After a few days: they become flat, with a livid red or purplish colour
Later: yellow or greenish appearance, similar to deep bruise, therefore named
‘erythema contusiformis’
▪ The eruption persists for 3–6 weeks & regresses leaving no residual marks

52. Variants:
▪ Erythema nodosum Migrans
▪ Subacute nodular migratory panniculitis ofVilanova and Pinol
▪ Chronic erythema nodosum

53. Investigation:
▪ complete clinical history
▪ enquiry about previous diseases, medications, foreign travels, pets
▪ complete blood count
▪ ESR
▪ ASO titre
▪ urinalysis
▪ throat culture
▪ intradermal tuberculin test
▪ chest X‐ray

54. Histopathology:
▪ Early lesions (less than 48 h ): Oedema and haemorrhage at the septa
and numerous neutrophils arranged interstitially between collagen
bundles
a) Septal panniculitis with thickened
connective tissue septa of the subcutis
b) Infiltrate at the septa is mostly composed of
neutrophils interstitially arranged between
collagen bundles

55. Histopathology:
▪ Miescher radial granulomas with small well‐defined nodular
aggregates of small histiocytic cells around a central stellate or
banana‐shaped cleft
a) fully developed erythema nodosum
thickened septa of the subcutaneous
tissue
b) Miescher radial granuloma:Aggregations of
small histiocytes around a central cleft

56. Histopathology:
▪ Late‐stage lesions : Septal fibrosis & periseptal granulation tissue,
partially replacing the fat lobules, with an infiltrate composed of
lymphocytes, histiocytes & multinucleated giant cells
a) late stage lesion with septal
panniculitis
b) Numerous multinucleated
giant cells are present in the infiltrate at
the septa

57. Histopathology:
▪ Fibrotic process involving the septa resolves completely after some
weeks or months.
a) very late stage lesion very thick
connective tissue septa at the
subcutis
b)The infiltrate at the interface shows
features of granulation tissue

58. Management:
▪ Treat the underlying cause, esp. if infectious
▪ It Regress spontaneously within a few weeks: Rest recommended
▪ Aspirin & NSAIDS,eg indometacin 100–150 mg daily or naproxen 500
mg daily (Exclude IBD)
▪ Potassium iodide 400–900 mg daily or solution of potassium iodide,
2–10 drops in water or orange juice thrice a day

59. Management:
▪ Prednisolone 40 mg/day or I/L injection of triamcinolone acetonide
10 mg/mL (Exclude infection)
▪ colchicine, 0.6–1.2 mg BD & hydroxychloroquine 200 mg twice a day
▪ anti‐TNF agents ( etanercept, adalimumab , infliximab for IBD)

60. ERYTHEMA NODOSUM LEPROSUM
ENL is a type II leprosy reaction which is characterized by a
necrotizing vasculitis involving small to medium‐sized vessels of
the deep dermis and subcutis.It is seen in patients with
MULTIBACILLARY LEPROSY(LL and BL)usually after initiation
of treatment.

61. PATHOGENESIS
It represents an immune complex‐mediated vasculitis secondary
to the deposition of large amounts of mycobacterial antigen,
immunoglobulins and complement in the vessel walls During
this type of reaction, patients show an increased CD4/CD8 ratio,
due to an increase inT-helper and a decrease inT‐suppressor
lymphocytes, accompanied by a specific increase inTh2
lymphocytes,which induce plasma cell proliferation and release
of immunoglobulins.

62. PATHOGENESIS

63. HISTOPATHOLGICAL FINDINGS IN ENL
Histopathological findings in ENL vary according to the age
of the lesions.
EARLY STAGE: nodules show oedema of the papillary
dermis and a neutrophilic infiltrate with necrotizing
vasculitis.
LATER STAGE: lesions exhibit a lymphohistiocytic
infiltrate, in which foamy macrophages with numerous
mycobacteria are seen within the fat lobule.

64. HISTOPATHOLGICAL FINDINGS IN ENL
Scanning power showing dense nodular
infiltrates in the dermis and mostly lobular
panniculitis
Some of the small capillaries of the fat lobule
show fibrin deposits and neutrophils involving
their vessel walls

65. A section of the same case stained with Ziehl–Neelsen stain. Higher
magnification of numerous microorganisms of Mycobacterium leprae within the
cytoplasmic vacuoles of the histiocytes.

66. ERYTHEMA INDURATUM OF BAZIN
Erythema induratum is a chronic recurrent reactive
disorder characterized by subcutaneous nodules located
preferentially on the posterior aspects of the lower legs of
adult women.The nodules commonly develop after
exposure to cold and may break down to form irregular
ulcers

67. CLINICAL FEATURES
EI/Nodular vasulitis is
recurrent,erythematous to
violaceous nodules and deep plaques
that may be tender but often are not
painful. Ulceration often leads to
scarring.Surface changes include
crusting of the ulcers and a
surrounding collarette of scale.

68. ETIOLOGICAL ASSOCIATIONS OF EI
• Chronic hepatitis C
• Ulcerative colitis
• Brucellosis
• Paraneoplastic process
• Nocardia infections
• Propylthiouracil
• SLE
• Chlamydophila pneumonia
• (BCG) Vaccination
• Aortic valve stenosis
• Hepatitis B
• Crohn disease
• Leukaemia
• Rheumatoid arthritis
• Hypothyroidism
• Cold weather
• Chronic venous insufficiency

69. PATHOGENESIS
1. ROLE OF MYCOBACTARIUM T.B: EI was frequently
associated with MTB, the etiology was controversial because
organisms are not always identified in the biopsies and tissue
cultures.With the advent of polymerase chain reaction
(PCR)techniques, multiple culture-negative cases were shown
to contain MTB DNA in 25%-77% of cases supporting the
pathogenic role of M.Tuberculosis.
2. HYPERSENSITIVITY REACTION:EI is considered to be a
hypersensitivity disorder mediated by immune

70. CONTD…
complexes(Type III) or cell-mediated hypersensitivity,
manifested by the presence of tuberculin skin tests and
highly positive interferon gamma release assay tests to
MTB.TheT cells, monocytes, and macrophages as well as
Langerhans cells may suggest a type(IV)hypersensitivity
reaction

71. HISTOPATHOLGICAL FINDINGS OF EI
EARLY LESION:
▪ There are discrete collections of
inflammatory cells, mostly neutrophils.
▪ There may be extensive necrosis of the
adipocytes of the fat lobule.
▪ These necrotic adipocytes elicit a response
from histiocytes, which phagocytose lipid
and become lipophages.
FULLY DEVELOPED LESION:
▪ Epithelioid and foamy histiocytes,
Langhans type or foreign‐body GCs and
lymphocytes contribute to the
granulomatous appearance.
▪ When intense vascular damage occurs, large
areas of caseous necrosis appear and the
lesions show all the histopathological
attributes of a tuberculoid granuloma.

72. EARLY LESION
Scanning power showing mostly lobular panniculitis
Higher magnification showing necrotic adipocytes
without nuclei and luminal thrombosis of a small blood
vessel

73. FULLY DEVELOPED LESION
Scanning power showing a mostly lobular panniculitis Small granulomas involving the fat lobule.

74. SCLEROSING PANNICULITIS
Sclerosing panniculitis is a relatively common form of
long‐term chronic panniculitis associated with chronic
venous insufficiency and typically affecting the lower
extremities of middle aged or elderly women.This is
manifested as a diffuse sclerosis and pigmentation of the
skin and subcutaneous tissue
(LIPODERMATOSCLEROSIS)

75. CLINICAL FEATURES
SP has an acute inflammatory stage and a chronic
fibrotic stage. In patients presenting with the acute
form, very painful, poorly demarcated, cellulitis-like
erythematous plaques persist and evolve to
violaceous,edematous, or indurated plaques or
nodules, which are seen on the lower legs, most
commonly on the lower anteromedial calf .

76. CONTD..
Chronic LDS presents as Indurated to
sclerotic, depressed and hyperpigmented
skin.These findings occur on the lower
portion of the lower leg, predominantly on
the medial aspect, or in a stocking
distribution.This is described as an
“INVERTEDCHAMPAGNE BOTTLE” OR A
“BOWLING PIN”APPEARANCE

77. HISTOPATHOLOGIC FEATURES
EARLY STAGE:
A sparse inflammatory infiltrate of
lymphocytes in the septa and areas of
ischaemic necrosis at the centre of the
fat lobules is seen. Necrosis of fat is
characterized by small pale anucleate
adipocytes.
FULLY DEVELOPED LESIONS: the
septa show marked thickening and
fibrosis,whereas lobules appear
atrophic, often with lipophagic
granuloma at their periphery. In this
stage, the inflammatory infiltrate is
composed of lymphocytes, histiocytes
and foamy macrophages.

78. HISTOPATHOLOGICAL FINDINGS
Scanning power showing thickened septa and cystic
spaces replacing the fat lobules
A cystic structure lined by a lipomembrane with a
crenellated border

79. CONTD..
Superficial dermis shows stasis changes Proliferation of thick‐walled capillaries and venules in
the superficial dermis.

80. CONTD..
A sectionof the same case stained with
periodic acid–Schiff (PAS).
PAS positivity of the pseudopapillae with feathery
projections into the cystic cavity.

81. CALCIPHYLAXIS
Calcific arteriolopathy (calciphylaxis) is strongly associated with
end‐stage chronic kidney disease and renal transplantation,
particularly in diabetics,though a small proportion of cases arise
in the absence of renal disease. Although the most common
areas of involvement are the lower extremities and
abdomen,the process may also involve other areas including the
genitalia.

82. CLINICAL FEATURES
It typically presents as irregular
exquisitely tender patches of mottled
dusky livedoid erythema with pale
greyishareas of devitalization before
progressing to full‐thickness infarction of
the skin with consequent necrotic
ulceration.These changes commonly
extend deeply into subcutaneous fat

83. PATHOGENESIS

84. HISTOPATHOLOGICAL FINDINGS
CALCIFICATION:
The most characteristic H/P finding consists
of small and medium‐sized vessel
calcification.Vascular calcification is usually
extensive within the vessel walls and often
exhibits a concentric,
circumferential,ring‐like pattern.
THROMBOSIS:
The involved vessels show luminal
thrombosis,develop intimal hyperplasia
with endovascular endothelial proliferation
and intimal fibrosis, resulting in ischaemia
of the areas.Secondary ischaemic changes
include epidermal ulceration and
degeneration of dermal collagen.

85. HISTOPATHOLOGICAL FINDINGS
Scanning power view showing involvement of the
vessels of deeper reticular dermis.
Calcification of the vessel walls and occlusion of the
vascular lumina.

86. HISTOPATHOLOGICAL FINDINGS
A section of the same case stained with
von Kossa stain.
Calcification of the vessel walls is
positive with von Kossa stain

87. COLD PANNICULITIS
▪ Cold panniculitis also know as “HAXTHAUSEN DISEASE”is a form of injury
to subcutaneous fat induced by exposure to cold, either environmental or as
cold objects applied to the skin (e.g. ice packs). Infants are particularly
susceptible.
▪ can occur on mucosa as well “POPSICLE PANNICULITIS”.
▪ When occurring in equestrians, the term “HORSE RIDER’S PERNIO”and
EQUESTRIAN PANNICULITIS are also used.

88. NEONATAL AND INFANTILE COLD PANNICULITIS
Neonates are particularly susceptible to cold
panniculitis,because subcutaneous fat in newborns is rich in
saturated fatty acids, particularly palmitic and stearic
acids, which have a higher freezing point so that a small
decrease in an infant’s temperature may result in
crystallization of subcutaneous fat.

89. CLINICAL FEATURES
In young children, the most commonly involved
areas are the cheeks and chin, because they are
rich in subcutaneous fat.The lesions consist of
indolent erythematous or violaceous indurated
plaques or nodules with no systemic
manifestations.The child is otherwise healthy and
the lesions regress without treatment within
weeks

90. COLD PANNICULITIS IN ADULTS
Adult patients with cold panniculitis are typically
obese female.The most commonly affected areas
are the lateral upper thighs and gluteal region.The
distribution of the lesions has been attributable to
the effects of tight‐fitting clothing compromising
the blood flow in the upper lateral thighs,
rendering the ischaemic fat more susceptible to
cold injury

91. HISTOPATHOLOGICAL FINDINGS
▪ H/P picture of cold panniculitis is a mostly lobular panniculitis,
with a lymphohistiocytic or mixed inflammatory infiltrate
present within fat lobules.
▪ There is a superficial and deep perivascular, as well as peri
adnexal, lymphocytic infiltrate with prominent inflammation of
veins most notable at the dermal subcutaneous fat junction
these H/P findings closely resemble those seen in perniosis. The
title“cold-associated perniosis of the thighs” has been
suggested.

92. HISTOPATHOLOGICAL FINDINGS
Scanning power showing dense nodular
infiltrates in deeper dermis
Small aggregate of lymphocytes in the fat lobule.

94. MANAGEMENT
▪ Cold panniculitis is self-limiting and resolves upon
rewarming without continued exposure to cold.Full
improvement may be seen over days to months.
▪ Prevention of infantile cold panniculitis in children is
achieved by avoiding cold exposure and direct contact
with ice products.
▪ For equestrian cold panniculitis in adult women, the use of
loose, warm clothing should be recommended when
riding, with avoidance of tight‐fitting clothes.
▪ In one case, a dramatic response to tetracycline was
observed, which was also effective prophylactically

95. LUPUS PANNICULITIS
Lupus panniculitis (LP),also termed LUPUS PROFUNDUS
and IRRGANG-KAPOSI SYNDROME, was first described
in 1883 by Kaposi and named lupus erythematous
profundus by Irrgang in 1940.

96. CLINICAL FEATURES
Clinically, lesions consist of
indurated plaques which
resolve with localized
lipoatrophy. Depending on the
intensity of inflammation
patient may first present with
lipoatrophy rather than
induration.The overlying skin
may show changes of chronic
cutaneous LE.The face, upper
arms upper trunk, breasts,
buttocks and thighs are most
commonly affected.

98. INVESTIGATIONS
H/P :LP is a predominantly lobular panniculitis in which the
infiltrate in active lesions involves mainly the fat lobule.The
septal component consists of thickening and sclerosis of the
collagen bundles in the septa.Active lesions exhibit a picture
of a predominantly lymphocytic panniculitis with numerous
plasma cells. Longstanding lesions show hyaline necrosis of
the fat lobule with little or no infiltrate and replacement by
diffuse eosinophilic glassy remnants of adipocytes

99. CONTD..
Lymphoid aggregates, sometimes with germinal centre formation, are also
frequently seen in the septa or at the periphery of the fat lobules.These
lymphoid follicles, although characteristic, are not pathognomonic of LP.
Additional histopathological findings consist
▪ Calcification,
▪ Interstitial mucin deposition
▪ Features of DLE in the overlying epidermis.
▪ Presence of nuclear dust within the infiltrate.
▪ Infiltrate of LP may contain some eosinophils

100. CONTD..
▪ Lymphocytic vasculitis consists of the presence of lymphocytes in and around the
vessel walls, mural fibrin deposition, luminal thrombosis and nuclear dust. Some
consider that hyaline necrosis of the fat lobule results from the ischaemic process
secondary to this lymphocytic vasculitis
▪ Calcification is also a frequent finding in chronic lesions of LP and consists of individual
calcification of elastic fibres or large masses of calcium within the lobules and septa.

101. CONTD..
Scanning magnification showing
predominantly lobular panniculitis.
Dense lymphoid aggregations at the interphase
between the fat lobule and the thickened septa

102. CONTD..
Hyaline necrosis involving the fat lobule
Reactive germinal centre formation within
the lymphoid aggregates.

103. CONTD..
▪ DIF:The lupus band test at the dermal–epidermal junction is
often positive.Additional findings consist of IgG deposition
at the periphery of adipocytes and around the vessels.
▪ IMMUNOHISTOCHEMICAL STUDIES:infiltrate in LP is
composed mostly ofT lymphocytes with a slight
preponderance of CD4 over CD8 lymphocytes.

104. CONTD..
▪ PCR ANALYSES:forTCRγ gene rearrangement in the
infiltrate has demonstrated its polyclonal nature in most
cases.
▪ Because of the presence of cytotoxic CXCR3+ lymphocytes
in the fat lobules, it has been suggested that lupus
panniculitis may be due to a type I interferonTh1 driven
immune response

105. TREATMENT
▪ Antimalarials, topical steroids.
▪ If active and severely inflamed, short courses of oral
corticosteroids.
▪ Other treatments inculde
Dapsone,thalidomide,cyclosporine,
methotrexate,IVIG,azathioprine,tacrolimus,
▪ Severe recalcitrant cases may require rituximab or
infliximab.

106. DERMATOMYOSITIS ASSOCIATED
PANNICULITIS
Panniculitis is less frequent in dermatomyositis than in LE and
systemic sclerosis Panniculitis has also been described in
juvenile dermatomyositis. In some patients, panniculitis is
associated with other characteristic cutaneous lesions of
dermatomyositis,whereas in others panniculitis is the only
cutaneous manifestation of the disease.

107. INVESTIGATIONS
▪ H/P: of dermatomyositis‐associated panniculitis are similar
to those of lupus panniculitis and consist of a
predominantly lobular panniculitis with lymphocytes and
plasma cells among the adipocytes.The septal collagen
bundles show hyaline sclerosis, and there is progressive
replacement of fat with fibrous tissue

108. CONTD..
Additional H/P findings include:
▪ Thickening of the blood vessels of the fat lobule
▪ neutrophilic vasculitis with fibrinoid necrosis or lymphocytic
vasculitis involving the arterioles of the septa
▪ calcification.
▪ Lymphoid follicles, with or without reactive germinal centre
formation but these finding s are less frequent .
▪ As in lupus panniculitis, there may be vacuolar change at the dermal–
epidermal junction and, in the late stages ofthe process,
membranocystic changes.

109. PANCREATIC PANNICULITIS
Panniculitis associated with and secondary to underlying pancreatic
disease was first noted in 1883.Variable pathologies of the pancreas
can induce panniculitis,including acute pancreatitis, even following
ERCP procedures.The panniculitis resolves as the pancreatic disease
improves, which may be difficult or impossible in cases of
malignancy.

110. CLINICAL FEATURES
The cutaneous lesions appear as
crops on the lower legs,especially
the periarticular areas, but are
also on the arms, wrists,thighs,
and trunk.The lesions are ill-
defined erythematous to red-
brown edematous and tender
nodules,which may involute and
resolve with atrophic
hyperpigmented scars.They may
have central “softer” areas or may
become fluctuant, abscess-like,
and drain an oily material

111. Extracutaneous manifestations
▪ Periarticular fat necrosis with concomitant arthritis and painful
medullary fat necrosis in bone. Monoarticular or oligoarticular
arthritis secondary to periarticular fat necrosis may be present in
more than ½ of patients. this triad of pancreatic
disease,panniculitis,and polyarthritis (ppp syndrome) is very
rare and is associated with both pancreatitis and pancreatic
carcinoma.
▪ Osteonecrosis may also develop as enzymes extend to the joint
capsules and cause purulent joints.

112. CONTD..
▪ Pleural effusions and serositis also may be seen with pancreatic panniculitis,and
pleural effusions are associated with a high mortality rate.
▪ Eosinophilia may be seen in pancreatic panniculitis resulting from either
pancreatitis or pancreatic malignancies.
▪ A pancreatic tumor(or pancreatitis)in association with
panniculitis,Polyarthritis,and eosinophilia (the schmid triad) imparts a poor
prognosis

114. PATHOGENESIS
Pancreatic panniculitis has generally been attributed to
release of pancreatic enzymes such as lipase, amylase, and
trypsin into the circulation, promoting vascular
permeability and damage, leading to release of fatty acids
from adipocytes and subsequent fat necrosis.However,
there are reports of pancreatic panniculitis in the setting of
normal serum levels of pancreatic enzymes.Resistin and
leptin are potential markers of extrapancreatic fat necrosis.

115. HISTOPATHOLOGICAL FINDINGS
EARLY LESIONS:Adipocytes lose their
nuclei but maintain peripheral
outlines,forming characteristic “ghost cells”
which are aggregated in small clusters at
the center of fat lobules,with a peripheral
inflammatory infiltrate of neutrophils
Saponification causes calcification,
producing fine,granular basophilic deposits
within and around necrotic adipocytess.
OLDER LESIONS:necrosis and ghost cells
are replaced by foamy histiocytes,
multinucleated giant cells, lymphocytes,
and, eventually fibrosis.

116. CONTD..
Scanning power showing a mostly lobular
panniculitis.
group of ‘ghost’ adipocytes surrounded by neutrophils
is seen at the periphery of the fat lobule.

117. TREATMENT
▪ The focus of treatment of pancreatic panniculitis is on the
underlying pancreatic disease.Care is often supportive.
▪ Octreotide a somatostatin analog,and plasmapheresis are
associated with resolution of pancreatic panniculitis.
▪ Treatingc pancreatic cancer with surgical resection and
combination chemotherapy may ameliorate the cutaneous
findings.

118. ALPHA‐1 ANTITRYPSIN DEFICIENCY
PANNICULITIS
Alpha‐1 antitrypsin deficiency is a genetic disorder that
manifests as pulmonary emphysema,liver cirrhosis and,
rarely, as cutaneous panniculitis. It is characterized by low
serum levels of α1‐antitrypsin, the main protease inhibitor
in human serum.

119. CLINICAL FEATURES
Painful erythematous nodules and
plaques, but early lesions may have a
cellulitic or fluctuant abscess-type
appearance.Lesions may ulcerate
with oily or serosanguinous discharge
and resolve with atrophic scars.The
lesions appear most commonly on
the lower trunk(buttocks)and
proximal extremities.

120. PATHOGENESIS
 Possible mechanisms leading to the development of 1AT panniculitis
include lack of interference with the various proteases that lead to
activation of autoinflammatory cascade mediated by activation of IL-1 ,and
lysis and destruction of connective tissue at sites of inflammation.
 Trauma to adipocytes may result in release of adipokines and cytokines
that are chemotactic to inflammatory cells,whose released proteases are
unopposed because of the absence of the 1AT, leading to severe damage in
involved tissue

121. INVESTIGATIONS
▪ Laboratory anomalies include absence or significantly reduced levels
of α1 globulin on plasma protein electrophoresis
▪ Abnormally reduced levels of α1‐antitrypsin.
▪ In chronic cases,normocytic normochromic anaemia and
hypoalbuminaemia are frequently found

122. HISTOPATHOLOGICAL FINDINGS
EARLY STAGE: presence of neutrophils extending into the
lower reticular dermis in an interstitial pattern between
collagen bundles (‘splaying of neutrophils’)
Occasionally,the intense neutrophilic infiltrate may cause
collagenolysis and elastic tissue destructions is seen at the
connective tissue septa and then necrotic fat lobules
appear to be ‘floating’ and surrounded by neutrophils.
Transepidermal elimination of liquefied dermis may occur
as a secondary phenomenon

123. CONTD..
LATE‐STAGE LESION: neutrophils and necrotic adipocytes are
less evident and the lesion is dominated by non‐specific
lipophagic granulomata replacing fat lobules. Some
macrophages may engulf nuclear dust of neutrophils and
dystrophic calcification may develop.
▪ DIF: shows deposits of complement C3 and IgM around the
dermal blood vessels: these are of uncertain significance

124. CONTD..
Scanning power showing involvement at the septa and
the periphery of the fat lobules
Neutrophilic infiltrate and nuclear dust but
no evidence of vasculitis.

125. MANAGEMENT
▪ Trauma and surgical debridement should be avoided
▪ Avoid smoking or exposure to hepatotoxins and eduction of alcohol
intake should be recommended.
▪ Doxycycline or minocycline in a dose of 200 mg daily for at least 3
months,may be effective in mild cases, as tetracyclines have
anticollagenase activity which may partly re‐establish
protease‐antiprotease homeostasis.
▪ Dapsone has also shown to be effective because it inhibits the
migration of neutrophils

126. CONTD..
▪ For severe cases with liver and lung involvement, the best
option is replacement of α1‐antitrypsin using human
pooled plasma from normal donors (ProlastinR).
Intravenous infusions in a dosage of 60–100mg/kg per
week, depending on the severity of the deficiency, over a
period of 3–7 weeks. Recurrence after discontinuation of
therapy is common, but there is a good response to
reinfusion.
▪ Other interventions which have been used include plasma
exchange and liver transplantation

127. Infective panniculitis

129. Cont.
▪ A wide variety of infectious agents has been reported to produce
panniculitis
▪ Some degree of immunosuppression is common
▪ Histopathological findings vary but often include mixed
septal/lobular panniculitis, neutrophilic infiltration,
hemorrhage and necrosis.

130. Treatment
▪ Treatment consists of appropriate antimicrobial therapy.
▪ Surgery may be indicated for isolated lesions

131. Neutrophilic lobular panniculitis
▪ Neutrophilic lobular panniculitis incorporates a range of different
panniculitides in which the fat lobule infiltrate is mostly composed of
neutrophils.

133. ▪ Subcutaneous Sweet syndrome
▪ Acute febrile neutrophilic dermatosis or Sweet syndrome is a
neutrophilic dermatosis characterized by an acute onset of edematous,
erythematous papules and plaques, often accompanied by fever and
malaise.
▪ The most frequent locations are the lower extremities, followed by
upper extremities, trunk and head.

134. ▪ Histopathological findings:
demonstrates a dense infiltrate of mature neutrophils involving
subcutaneous tissue.The neutrophilic infiltrate may involve septa,
lobules or both, without vasculitis.
▪ Management :
Systemic corticosteroid and dapsone

135. FACTITIOUS PANNICULITIS
▪ Factitious or artefactual panniculitides result from external injury to
subcutaneous fat.
▪ Aetiological factors includes
mechanical trauma,
chemical substances and
thermal injury

136. ▪ The injurious events may be accidental, purposeful or iatrogenic, and it may be a
manifestation of a underlying psychiatric disturbance.
▪ Extrinsic injury can produce panniculitis. There are four categories :
Cold panniculitis
Sclerosing lipogranuloma
Panniculitis due to other injectables or therapies
Panniculitis due to blunt trauma

138. Microscopic features

139. Management
▪ Early lesions of factitious panniculitis should be treated with systemic
antibiotics to cover a wide spectrum of microorganisms
▪ If artefact is suspected, the affected area may be occluded for a week with
a bandage: improvement would support a suspicion of self induced
factitious panniculitis.
▪ Panniculitis secondary to cosmetic fillers usually require intralesional
steroids
▪ Panniculitis secondary to injection of drugs usually requires only supportive
care and withdrawal of the responsible drug

140. Subcutaneous fat necrosis of the
newborn

141. Subcutaneous fat necrosis of the
newborn
▪ It is a localized process occurs in full term neonates during the first 2 -
3 weeks of life.
▪ Precipitating factors:
 Hypothermia,
 hypoglycemia,
 perinatal hypoxemia,
 increased ratio of saturated: unsaturated fatty acid

142. Clinical features
▪ The lesions consist of multiple symmetrically distributed
indurated, smooth, non‐pitting mobile subcutaneous
erythematous or violaceous nodules or plaques that appear in
the first few weeks of life.
▪ The most common locations are the shoulders and
buttocks.

143. Complications:
▪ Hypercalcemia
▪ Transient thrombocytopenia, probably due to platelet sequestration
▪ Hypoglycemia due to maternal diabetes
▪ Hypertriglyceridaemia
▪ Nephrocalcinosis

144. Histopathological findings :
▪ subcutaneous fat necrosis of the newborn shows a lobular panniculitis,
with a dense predominantly inflammatory infiltrate composed of
lymphocytes, histiocytes, lipophages, multinucleate giant cells with fat
necrosis.
▪ doubly refractile narrow needle‐shaped clefts radially arranged, which
represent triglyceride crystallization within adipocytes and stain with oil
red

145. Management
▪ Lesions resolve spontaneously.
▪ Supportive care is required
▪ Hypercalcemia is managed
 by hydration
 Dietary restriction of both calcium and vit D
 Furosemide
 Calcitonin and bisphosphonates

146. Post steriod panniculitis
▪ Poststeroid panniculitis is a rare panniculitis of children and infants, is
related to a rapid decrease or a sudden withdrawal of steroid therapy
▪ ages ranging from 20 months to 14 years
▪ The lesions vary in size from 0.5 to 4 cm and consist of asymptomatic
firm subcutaneous nodules, often with overlying erythema, and tend
to be localized in those areas where there is the greatest
accumulation of fat from steroid therapy, such as the face, arms and
posterior neck.

147. Cont.
▪ They usually appear 1–10 days after cessation of high doses of
systemic corticosteroids.
▪ Histopathological findings:
lobular pannniculitis with lymphocytes, macrophages,
multinucleated giant cells; needle shaped clefts in lipocytes
and giant cells

148. Treatment
▪ no treatment is usually necessary, lesions usually
disappear gradually without residual scarring
▪ However, re administration of high doses of systemic
corticosteroid and a slower and more gradual decrease of
the dose is followed by a faster improvement and
resolution of the lesions.

149. Sclerema neonatorum

150. Cont.
▪ Sclerema neonatorum is an uncommon condition which typically
affects gravely ill, preterm neonates in the first week of life.
▪ It manifests as a diffuse hardening of skin and subcutaneous tissue
▪ It is associated with a high mortality

151. ▪ Appear severely ill from birth and during the first days of life
▪ They develop generalized woody induration of the skin
▪ Usually, the process begins on the buttocks and thighs but rapidly extends to
involve almost the entire skin surface with the exception of the palms, soles and
genitalia.
▪ The involved skin has a hard consistency, is non‐pitting and is cold to the touch; it is
yellowish‐white in colour, often with purplish mottling.
▪ There is immobility of the extremities and the face shows a mask‐like expression.
▪ The prognosis is poor and most affected infants die within a few days.

152. Histopathology

153. Management
▪ Treatment of sclerema neonatorum is mainly directed to the
underlying disease.
▪ Attempts to treat this disorder are disappointing.
▪ Supportive treatment

155. Gouty panniculitis

156. ▪ Panniculitis is a very uncommon complication of tophaceous gout.
▪ clinical presentation consists of painful ulcerating nodules on the lower
legs.
▪ Histopathology shows a lobular, sometimes neutrophilic panniculitis
with deposition of needle‐shaped refractile crystals within adipocytes

157. Cytophagic histiocytic panniculitis and
subcutaneous panniculitis‐like T‐cell
lymphoma

158. Cont.
▪ The term cytophagic histiocytic panniculitis was introduced to describe
a rare entity characterized by the development of subcutaneous nodules
containing lobular infiltrates of macrophages which had phagocytosed
lymphocytes, erythrocytes and nuclear debris

159. Cont.
▪ patients present with erythematous subcutaneous nodules
that may group into large plaques typically involving the
lower extremities .
▪ A common feature consists of areas of lipoatrophy when
the lesions resolve.
▪ Approximately, 50% of patients have B symptoms,
including fever, fatigue and weight loss; cytopenia and
elevation of liver enzymes are frequently found.

160. ▪ Histopathological findings:
Mostly lobular panniculitis without vasculitis
Histiocytes and mature lymphocytes within fat lobules with
necrosis of adipocytes. Bean –bag cells: macrophages that
contain intact or fragmented erythrocytes, leuckocytes or
platelets within their cytoplasm

162. ▪ Treatment
Immunosuppression with cyclosporine and corticosteriods.
Other options include tacrolimus, AZA, anakinra, cyclophosphamide
with IVIG.