Diseases of Subcutaneous Fat. Endocrine Diseases.

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Diseases of Subcutaneous Fat. Endocrine Diseases.

• Michael Hohnadel
• KCOM
• 1/20/04

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Diseases of Subcutaneous Fat

• Panniculitis
• May appear similar due to depth
• Two broad categories
• Septal (classically E.N.)
• Lobular (Vascular)

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Erythema Nodosum

• Acute Erythema Nodosum
• Crops of bilateral, deep, tender, 1-10 cm
  diameter, red nodules, on pretibial area (or
  other). Lesions resolve over several days or
  weeks, leaving a bruise like area. (erythema
  contusiforme) which resolves without scarring.
• Fever, malaise, leg edema, arthritis and other
  systemic symptoms may be present
• Associated states (reactive process)
• WgtgtM, TB, Streptococcal inf., Yersinia,
  Salmonella, deep fungal infections, Sarcoidosis,
  drug (oral contraceptives). Pregnancy. Many
  others.

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Erythema Nodosum

• Chronic Erythema Nodosum
• Distinguishing features
• Older women
• Unilateral, Single lesion which spreads
  centrifugally to form annular plaques. Sometimes
  bilateral.
• No systemic symptoms ( Possibly arthralgia )
• Less tender
• No underlying disease
• Prolonged course of months / years.
• Key to diagnosis Pretibial, no systemic
  complaints. Biopsy seldom required.
• DDX erythema induratum (post. Calf), syphilitic
  gummas (unilateral). Subcutaneous fat necrosis
  assoc with pancreatits ect. systemic.

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Erythema Nodosum
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Erythema Nodosum

• Histologic Features
• Septal infiltrate of neutrophils (early), other
  mononuclear cells. Histiocytes and Multi Giant
  cells may predominate older lesions. Some foamy
  histiocytes may be seen.
• Meischers radial granulomas Aggregates of
  histiocytes around stellate clefts is
  characteristic not diagnostic.

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Erythema Nodosum
Infiltration of inflammatory cells between the
adipocytes
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Erythema Nodosum
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Erythema Nodosum

• Treatment
• Treat underlying causes.
• NSAIDS, bed rest / reduced activity
• Potassium Iodide Increase to control.
• Watch for hypothyroidism.
• Intralesional / systemic Steroids
• Refractory cases anti-malarials, colchicine.
• Most cases resolve in 3-6 wks.

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Nodular Vasculitis

• Tender subcutaneous nodules of calves of middle
  aged, thick legged women. Bilateral, often
  ulcerate and recur over years.
• Pathology Arteritis, venulitis of septal vessels
  with substantial necrosis of lobular adipocytes
  resulting in suppuration and perforation.
  Granulomatous inflammation.
• DDX Erythema induratum. TB testing, PCR of
  affected tissue for mycobacterium.
• Treatment SSKI (50 effective). Other agents
  used in E.N.

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Nodular Vasculitis
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Sclerosing Panniculitis(Lipodermatosclerosis)

• Presentation Development of woody induration of
  lower calves (esp. left) with appearance of
  inverted champagne bottle. Induration begins near
  ankles and slowly progresses proximally. Most
  common W gt 40 years. May be painful.
• Pathogenesis venous insufficiency with hypoxia
  of center of fat lobule. May not be apparent
  venous disease.
• Histopathology Necrosis of fat lobules with
  ghost cells (pale cells no nuclei). Foamy
  histiocytes, inflammatory cells and septal
  thickening with fat microcyst.
• Biopsy should be avoided. Heals poorly. Venous
  eval.
• TX - Treat venous insufficiency.
• Compression stockings (may be painful).
• Stanozolol decreases perivascular fibrin,
  decreases pain in 3 wks and induration in 8 wks.
  

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Sclerosing Panniculitis
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Physical Panniculitis

• Sclerema Neonatorium
• Presentation Gravely ill, premature neonates
  skin begins to harden on buttocks and LE and
  rapidly spreads to involve entire body except
  palms, soles and genitalia.
• Mobility affected by induration.
• Rapidly fatal.
• Child is very ill.
• Histopathology Enlarged adipocytes filled with
  needle like clefts in radial array.
• TX treat underlying disease.

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Sclerema Neonatorium
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Subcutaneous Fat Necrosis of the Newborn.

• Presentation Asymptomatic, firm, rubbery nodules
  on upper back, buttocks, cheeks and proximal
  extremities. May fuse into plaques which resolve
  over several months without scarring.
• Occurs during first 4 weeks of life.
• Child is otherwise healthy
• Associated with perinatal hypothermia, asphyxia
  and difficult labor and maternal drug use.
• Rarely, hypercalcemia occurs during the episode.
• Histopathology Lobular panniculitis with radial
  needle clefts in adipocytes.
• Fine needle aspiration has been used to DX.

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Subcutaneous Fat Necrosis of the Newborn.
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Subcutaneous Fat Necrosis of the Newborn.
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Cold Panniculitis

• Synonyms Popsicle / equestrian panniculitis.
• Presentation Within several days of cold
  exposure, affected skin becomes mildly
  erythematous with nontender firm Sub-Q nodules.
  Face, thighs and scrotum.
• Typical patients (Hx of cold exposure).
• Infants and young children. Black gt Whites.
• Scrotal disease prepubertal, 9-14 yr old male
  who is over weight. Bilateral, painful, no
  transillumination.
• Resolves in several days to weeks without TX.

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Cold Panniculitis
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• Post Steroid Panniculits
• Firm sub-Q nodules form within one month of rapid
  withdraw from high dose systemic steroids.
• Predominantly children.
• Most cases resolve. May have to restart steroids
  and wean more slowly.
• Traumatic Panniculitis
• Trauma, often not recalled, induces a firm mildly
  tender lipoma like sub-Q mass.
• Heals with fibrosis of septa.

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• Factitial Panniculitis
• Factitial injection of foreign substances into
  the skin. Medical personal are common patients.
• DX
• Careful HX. Fits no other pattern.
• Healing injection site, biopsy revealing foreign
  material, polarized light micro, Mass
  spectroscopy in difficult cases is suspicion is
  high.

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Sclerosing Lipogranuloma

• Granulomatous and fibrotic reaction from
  intentional, often cosmetic, injection of mineral
  oils, silicon or guayacol (Mexico).
• Presentation Up to ten years after implantation,
  skin becomes erythematous, hyperpigmented and
  indurated with a lumpy quality of sub-q. Due to
  migration of material, features may extend beyond
  the implantation site.
• 66 autoimmune finding () ANA, Raynauds,
  Sjogrens ect. 10 connective tissue disease
  usually scleroderma.
• Histologically Swiss cheese appearance of
  panniculus. Histiocytes with ingested material.
  Fibrosis.

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Sclerosing Lipogranuloma
2nd to Cosmetic Paraffin injections
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Sclerosing Lipogranuloma
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Pancreatic Panniculitis

• Fat necrosis 2nd to Pancreatitis or pancreatitc
  carcinoma. May be first sign of malignancy (40).
  Digestive enzymes cause damage.
• Presentation Tender or painless, erythematous
  Sub-q nodules 1-5 cm. In diameter. Lower leg is
  affected 90. Lesions typically number lt10 (may
  be 100s). Involutes with scarring.
• Assoc findings abd pain (sometimes), arthritis
  (FFA in synovial fluid), pulm. infiltrates.
• DX pancreatic workup amylase, lipase.
• Peripheral eosinophila in Pancreatic CA.
• Histology fat necrosis, Ghost cells. Finely
  stippled Basophilic material (Calcium) with rim
  of necrotic cells. Inflammatory infiltrate at
  periphery.

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Pancreatic Panniculitis
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Pancreatic Panniculitis
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Alpha-1 Antitrypsin Deficiency Panniculitis

• 12500 of European decent have homozygous
  deficiency of enzyme which inhibits neutrophil
  elastase. The genetic defect results in a
  molecule that cannot be released from its
  production sites in hepatocytes.
• AAT is 1 of the 3 most common lethal genetic
  diseases among whites.
• Presentation After minor trauma, painful nodules
  appear on extremities and trunk. Lesions may form
  draining sinuses.
• MF, 20-40 years.
• Histopathlogy Dissolution of septae. Islands of
  normal fat floating in spaces of destroyed septae.

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Alpha-1 Antitrypsin Deficiency Panniculitis
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Alpha-1 Antitrypsin Deficiency Panniculitis

• DX
• Constellation of Liver dysfunction and Pulmonary
  dysfunction with skin lesions
• Serum AAT levels
• AAT function analysis
• TX
• Replace enzyme (prolastin)
• Dapsone, doxycycline

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Cytophagic Histiocytic Panniculitis

• Multi-system disease with widespread, painful
  sub-q nodules which may break down and form
  ulcerations.
• Progressive febrile illness with heptomeg,
  pancytopenia, HTG.
• Etiology Proliferation of histiocytes. Triggered
  by viral infection or 2nd to lymphomas.
• Benign (-) EBV
• Malignant () EBV, B or T cell Lymphoma.
• HIV assoc.
• Histopathology Infiltration of fat lobules with
  histiocytes with fat necrosis. Bean bag cell
  stuffed with RBC.
• Clonal B or T cell proliferation malignant.
• TX Benign - cyclosporine induces permanent
  remissions. Malignant - Chemo or bone marrow.

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Cytophagic Histiocytic Panniculitis
Subcutaneous nodules with purpura
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Cytophagic Histiocytic Panniculitis
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Misc. Panniculitis

• Eosinophilic Panniculitis
• Prominent infiltration with eosinphils assoc with
  arthropod bites, parasites, contact derm, Wells,
  bacteria, injections.
• Gouty Panniculitis
• Uric acid in Sub-Q leading to fat necrosis.

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Lipoatrophies

• Total
• Partial
• Centrifugal
• Semicircular
• Lipoatrophia Annularis
• Localized
• HIV associated

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Total Lipodystrophy

• 2 types Congenital vs Acquired.
• Both are assoc. with D.M. (lipoatrophic diabetes)
• 1.) Beradinelli - Seip (congenital)
• Autosomal recessive. Hypermetabolic state.
• General Paucity of fat at birth with voracious
  appetite, increased height velocity, muscular
  hypertrophy, genital enlargement, mild MR,
  protuberant abdomen, HTG. Hypertrophic
  cardiomyopathy, pul stenosis. DM resistant to
  therapy.
• Cutaneous AN (often generalized), Hypertrichosis
  with abundant curly scalp hair.
• Death in young adulthood from DM, cardiac, liver
  dx.
• TX fenfluramine reduces hypermetabolic state.

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Beradinelli - Seip (congenital)
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Congenital Total Lipodystrophy
AN and Loss of Bichats fat pad
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Total Lipodystrophy

• 2.) Seip - Lawrence (acquired)
• Begins lt15 yrs old, often lt5yrs (not at birth)
• Well defined illness precedes 30 of cases.
• Presentation As in congenital, but less
  striking. AN with DM is common. Severe liver
  involvement is more common (death). Loss of fat
  may begin local and generalize or start
  generalized.
• TX etretinate has helped AN in some.

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Seip - Lawrence (acquired)
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Partial Lipodystrophy

• (Inherited Forms)
• Kobberling-Dunnigan syndrome
• Autosomal dominate.
• At puberty adipose tissue is lost from
  extremities, gluteal and truncal areas with fat
  accumulation on the neck and face.
• DM with AN, HTG, hirsutism, PCOS after age of 20
  years.
• Other inherited forms
• Onset early infancy with adipose tissue loss
  localized to the face and buttocks. Rieger
  anomaly tooth and eye abnormalities hypoplasia
  of the iris and iris strands to the peripheral
  cornea.
• Bone age and dentition are retarded.
• DM late. No AN.

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Partial Lipodystrophy

• (Acquired Forms)
• Progressive Partial Lipo. (Barraquer-Simons)
• W gt M, Present first or second decade.
• After a febrile illness, diffuse and progressive
  loss of fat beginning on face and scalp and
  progressing downward to iliac crest. Sparing of
  LE.
• No discomfort or inflammation.
• Low C3 levels are assoc. and proteinuria occurs
  in in 50 of these cases.
• 3rd trimester intrauterine death may occur.

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Progressive Partial Lipo.
Loss of buccal fat and AN.
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Lipoatrophies

• Centrifugal
• One type is seen primarily in infants from Japan.
  90 are under 5 years.
• Centrifugally spreading loss of abdominal fat
  over 3- 8 years with regional lymphadenopathy.
• Resolves completely after progression stops.
• Semicircular
• Adult women affected with single or multiple,
  asymptomatic, symmetric depressions of
  anterolateral thigh.
• Often after trauma. Resolves in several years.
• Annular Atrophic panniculitis
• 10cm band of atrophy, bilaterally, around the
  ankles of children and young adults. Rare.

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Lipoatrophies

• Lipoatrophia Annularis
• Bracelet like constrictions of upper extremities
  1-2 cm wide on women following a period of
  swelling and erythema of extremity.
• Arthralgias and Pain of affected extremity
• Persist up to 20 years.
• Localized lipodystrophy
• 2nd to injection of medications esp. insulin.
• HIV assoc. Lipodystrophy.
• Occurs in effectively Treated Aids Patients with
  reverse transcriptase inhibitors and protease
  inhibitors.
• Fat redistribution from face, buccal, buttocks
  and limbs is lost to neck , upper back and inter
  abdominal areas.

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Localized lipodystrophy
Insulin injection lipodystrophy
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HIV assoc. Lipodystrophy
Loss
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• Endocrine diseases

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Acromegaly

• Hypersecretion of growth hormone.
• 2nd to adenoma
• Changes
• Diffuse hypertrophy of skin. Reddening and
  wrinkling of forehead.
• Cutis verticis gyryata in 30
• Enlargement of hands and feet and tongue.
  Drum-stick fingers.
• Hypertrichosis, hyperpigmentation, hyperhydrosis.
• TX transpenoidal microsurgery. Irradiation.
  Octreotide inhibits GH if surgery is not an
  option.
• 50 of patients completely normalize with TX.

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Acromegaly
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Cushings Syndrome

• Hyperfunctioning of adrenocortical tissue
• Cushing disease microadenoma of pituitary. 10
• Hyperfunctioning adrenals/adenomas or other
  tumors account for remainder.
• Non Iatrogenic W gt M. Peak age 20-30s.
• Features
• Obesity of face, neck and trunk. Buffalo trunk.
  Moon face
• Cutaneous hypertrichosis, dryness, fragility,
  acne, dermatphyte/pityrosporum infections,
  flushing, striae of abdomen and thighs. Thinning
  of skin.
• Systemic HTN, weakness, reduced bone density,
  DM, atherosclerosis, osteoporosis.

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Cushings Syndrome
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Cushings Syndrome
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Addisons Disease

• Adrenal insufficiency
• Increased Pituitary POMC leads to increased ACTH
  and melanocyte stim. hormone.
• Cutaneous signs
• Diffuse hyperpigmentation
• Most prominent in sun exposed areas and sites of
  recent trauma
• Axillae, perineum and nipples.
• Darkening of palmar, scars, hair and nails.

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Addisons Disease
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(No Transcript)
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Panhypopituitarism

• Loss of pituitary hormones 2nd to infections
  (syphilis and TB), tumor, postpartum hemorrhage.
• Loss of melanin 2nd to decreased ACTH/MSH.
• Cutaneous signs Thin dry skin. Diffuse loss of
  body hair. Thin, opaque, slow growing nails.
  Light skin susceptible to sunburn. Decrease in
  facial folds.

Fine facial wrinkles and light skin
Diminished axillary hair is an early sign
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Hypothyroidism

• Cretinism
• Insufficient thyroid hormone in fetal life
• Cool, dry, white to yellow skin. Patchy alopecia.
  Hypohydrosis. Brittle nails. Thick protuberant
  lips. Enlarged tongue. Wide face.
• Myxedema
• Systemic mucinosis
• Rough, dry, dull skin over areas of swelling, esp
  the face. (lips, tongue and nose)
• Diffuse hair loss and shedding of outer third of
  eyelashes occurs
• Brittle, coarse nails.

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Hypothyroidism
Pretibial Myxedema with peau d orange of mucin
deposition
Cretinism
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Hypothyroidism

• Mild Hypothyroidism
• Harder to detect
• Coldness of hands and feet in absence of vascular
  disease, cool intolerance, hypohydrosis, Weight
  gain, excessive sleeping, constipation.
• Palmoplantar keratoderma may occur and resolves
  with TX.

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Hypothyroidism

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Hypothyroidism
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Hypothyroidism
Palmoplantar keratoderma
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Hyperthyroidism

• Cutaneous changes
• Warm, moist, smooth textured skin.
• Thin, downy hair with possible non-scarring
  alopecia.
• Diffuse pigmentary changes - melanoderma. may
  result in melasma.
• Plummerss nails concave with distal
  onycholysis.
• Graves disease (FgtM, onset 20-30 years.)
• Thyroid Acropachy ( 1 of graves patients)
• Digital clubbing, diaphyseal proliferation in
  acral and distal bones.
• Frequently accompanies exophthalmos and pretib.
  myxedema
• May be seen in euthyroid and hypothyroid pt on
  occasion. Acromegally, Pul. osteoperiostitis.
• Radiographic findings are pathognomonic.

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Thyroid Acropachy
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Hyperthyroidism

• Pretibial Myxedema
• 4 of graves patients. Also, during Hashimotos
  thyroiditis and primary hypothyroidism.
• Bilateral, localized accumulations of
  glycosaminoglycans assoc with thyroid stimulating
  antibodies.
• Exophthalamous and acropachy assoc.
• TX
• intralesional steroids, clobetasol under
  occlusion. (not systemic)
• IVIG
• Vitiligo 7 assoc with graves.

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Hyperthyroidism
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Hypo-parathyroidism

• Cutaneous
• Poor dentition if during development.
• Dry scaly skin.
• Scanty hair. Absence of axillary and pubic hair.
• Brittle malformed nails with onycholysis.
• 15 of idiopathic cases develop candidisis.
• APECED syndrome
• Autoimmune PolyEndocrinopathy, Candidasis,
  External Dystrophy - syndrome.
• Hypoparathroidism most common endo. Dysfunction
  with this syndrome.

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Pseudo - hypoparathyroidism

• Autosomal dominate or X-linked.
• End organ unresponsiveness to PTH.
• Elevated PTH and phosphorus. Low calcium.
• Clinical findings
• Short stature, obesity, round face, prominent
  forehead, low nasal bridge, attached ear lobes,
  short neck, short wide nails, delayed dentition,
  mental deficiency, blue sclera and cataracts.
  Sub-Q calcifications
• Shortened long bones 2nd to premature epiphyseal
  closure.
• Short stubby toes with metacarpophalangeal
  dimpling (Albrights sign).
• Albrights hereditary osteodystrophy
• Includes Pseudo-hypoparathyroidism and
  Pseudo-pseudo PH.
• Defect in G protein pathway leads to resistance
  to agents acting through adenylate cyclase
  pathway.

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Albrights Hereditary Osteodystrophy
Features of Albright Hereditary Osteodystrophy
(AHO). A Young woman with short stature ( 3rd
centile), disproportionate shortening of the
limbs, generalized obesity, and round, flattened
face. B Radiograph of the hand showing the
shortened 4th and 5th metacarpals. C Fist with
the characteristic 'dimples' over the 3rd, 4th,
and 5th digits replacing the knuckles formed by
the distal head of normally sized metacarpal
bones (Archibald sign). D Brachydactyly of the
hand, with the short 4th and 5th digits, the
greatly foreshortened terminal 1st digit, and
very short, wide thumbnail (potter's thumb).
(Reproduced from Levine, 2000, with permission).
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Hyper-Parathyroidism

• Multiple endocrine neoplasia (MEN-I)
• Tumors of Parathyroid, pancreas, pituitary,
  thyroid and adrenal glands.
• Most common abnormality is hypercalcemia from
  the tumors of the parathyroids.
• Autosomal dominate. Presents in 4th decade.
• Assoc. with multiple angiofibromas, collaganomas,
  café au lait macules, lipomas, confetti like
  hypopigmentation and gingival macules.
• Tumors arise 2nd to abnormal tummor suppresor
  genes

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Hyper-Parathyroidism and MEN-I
Angiofibromas
Collagenomas
Gingival papules
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Acanthosis Nigricans

• Hyperpigmentation and papillary hypertrophy in a
  symmetrical distribution. Any area of the body
  may be involved including conjunctiva, lips and
  buccal mucosa. Palms may show hyperkeratosis.
• Type I Malignancy associated.
• Preceeds(18), accompanies(60), follow(22)
  malignancy
• Adenocarcinoma most associated. Esp G.I.
• Nonobese male gt40 yrs old.

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Malignant Acanthosis Nigricans
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Acanthosis Nigricans

• Tripe Palms thickened velvety palms with
  demoglyphics.
• 95 assoc with cancer.
• 77 occurs with AN.
• If only palms were only presenting sign then lung
  CA most common.
• If palms and AN then gastric cancer most common.
• Type II Familial Acanthosis Nigricans.
• Present at birth or early childhood.
• No cancer assoc.
• Accentuated at Puberty.

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Tripe Palms
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Acanthosis Nigricans

• Type III DM assoc.
• Most common
• Grayish, velvety thickening of neck, axillae and
  groin.
• Occurs in obesity and with endocrine disorders
  such as DM, acromegaly, Stein Leventhal,
  Cushing, Addisons, thyroid d/o. Renal transplant
  pts. Many others.
• Insulin resistance either clinical or subclincal.
• Drugs nicotinic acid, glucocorticoids,
  diethylstilbestrol, trizineate, BCP.

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Acanthosis Nigricans
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Acanthosis Nigricans

• Histopathology papillomatosis, hyperkeratosis
  and slight hyperpigmentation. Without thickening
  of the Malpighian layer.
• Darkening of skin 2nd to hyperkeratosis.
• Treatment
• Address malignancy, endocrinopathy
• Weight Loss
• Lipodystrophic DM improves with fish oil.
• Etretinate and tretinoin.

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• The End