Panniculitis: inflammatory disease of subcutaneous fat. Clinically all present as subcutaneous nodules.

Can separate EN (septal panniculitis) from lobular panniculitidies. Need incisional biopsy or double punch. Septal panniculitis (acute and chronic EN): most common inflammatory panniculitis. 1. EPI: F:M 3-6:1 2. Clinical: bilateral, symmetrical, deep tender nodules and plaques. a. Lesions on upper legs, arms, neck, and face possible. b. Associated with malaise, leg edema, arthritis/arthralgias. c. Fever, HA, episcleritis, conjucnitivitis, GI complaint may be possible. d. Acute: reactive process i. Streptococcal infection. ii. Tuberculosis iii. Yersinia, Salmonella, Shigella intestinal iv. Systemic fungal infections v. Toxoplasmosis. vi. Sarcoidosis: fever,cough, joint, hilar adenopathy (Lofgren syndrome). Usually self limited course. vii. Inflammatory bowel disease (Crohns>UC). Associated more with female, eye, joint, isolated colon involvement. e. Drugs: i. Bromides, iodides, sulfonamides ii. OCPs iii. Echinacea iv. Infliximab in ankylosins spondylitis. f. Bechets & Sweets sydnrome. In former may be primary vasculitis. 3. Chronic EN: a. Older women b. Unilateral or asymmetrical c. No other systemic than arthralgias d. Painless/less tender e. Not associated with underlying disease f. Prolonged course of months to yeras. 4. Differential: EI affects posterior calves with ulceration and scarring. a. Syphilitic gummas unilateral b. Subcutaneous fat necrosis. c. Subacute infectious process 5. Histology: Septal panniculitis. Mixture of neutrophils early or lypmhocytes then more mixexd. LCV not histologic feature. 6. Management: a. Identify trigger, rest and elevation of affected extremities, anti-inflammatoyr medicaitons. b. ASO titre c. 4% of patients with histo present with EN. d. Treatment of infection does not shortne duration of EN. e. Bed rest is of great value, especially in children, support hose. f. Treat: i. ASA, nSAIDS ii. Potassium iodide five drops 3x day increased by one drop per dose per day. Watch for induction of hypothyroidism.

iii. IL corticosteroids, systemic steroids. iv. Colchicine for acute lesions. 7. Prognosis: Good, 3-6 week duration. Recurrences can occur iwth repeat infection or if physical activity resumed too quickly. Lobular Panniculitis 1. Vessel based lobular panniculitis: inflammation of thrombosis of blood vessels may lead to fat necrosis due to ischemia. Can occur in primary vasculitis or metabolic disease with deposition. Nodular vasculitis: identcal to EI (latter defined as prsence of TB). 1. Clinical: Calves of middle aged thick legged woemn. Bilateral and less red and tender than EN, can ulcerate, drain oily liquid, recur over years. 2. Vasculitis not required for diagnosis, get inflammation and necrosis of fat through epidermis forming ulceration. 3. Non-tuberculous nodular vasculitis can be differentiaed by looking for TB in patietn via skin tests. CPR with Tb DNA in 50-70% of EI. Manifestation of cellular immunity to TB so PPD always positive. Rare, only 1% of cutaneous manifestations of TB in one study. 4. Treat: underlyin TB or SSKI if not TB. Effective in half of cases, otherwise colchicine, antimalarials, NSAIDS, MMF. ---------Sclerosing Panniculitis: Occurs on medial lower third of lower legs of older obese women. May be bilateral. Left leg usually favored over right. Marketd woody induration that results from fibrosis in subcutaneous fat which may occur without original inflammatory panniculitis ever being observed. 1. Cause is venous insufficiency with varicosities, thrombophlebitis, DVT. May have procoagulant genetics. Venous insufficiency results in hypoxia, fat necrosis, inflammation, fibrosis. If other cause of hypoxemia present may get worse isease. 2. Histology: Stasis overlying lesions. Ischemic necrosis in center of fat lobules with ghost cells leading to mixed inflammatory infiltrate. Fat microcysts. 3. Treatment: Graded compression stockings and elevations. Pressure dressings like unna boot. a. Pentoxyfylline b. Stanazol to enhance fibrinolytic capacity of affected patients, may induce hepatitis. Can be virilizing. c. Surgical treatment can lead to dramatic improvement in some patients. ---------Physical Panniculitis: Infants and children most affected, caused by metabolic differences in fat. 1. Sclerema Neonatorum: Affects premature neonates who are gravely ill. Affected neonates usually die. Skin hardens, first on buttocks/lower extremities then spreads. ? Exchange transfusion as helping. Needle like clefts with sparse inflammation on histology. 2. Subcutaneous fat necrosis of newborn: During first 4 weeks (1/2 first week). a. History: fetal distress, birth asphyxia, meconium.

b. Maternal: cocaine use, neonatal anemia, thrombocytopenia, septicemia, hypothermia. c. Lesions fuse to form plaques, resolve spontaneously within 3 months with no scarring. d. Systemic: hypoglycemia, thrombocytopenia, hypertryglyceridemia, lactic acidosis, hypercalcemia (50%).Check calcium for 3-4 months. e. Pathogenesis: may be elevated prostaglandin E levels or high 1,25 D. Steroids, calcitonin, bisphosphonates. f. Histology: lobcular panniculitis with needle-shaped clefts. 3. Cold Panniculitis: Infants and young children predisposed. Popsicle panniulitis or scrotum of prepubertal males. Equestrian panniculitis is perniosis. Usually scrotum in obese 9-14 year old male, guarded and broad-based gait. Cryptorchidism possible. ----Post-steroid panniculitis: in children treated acutely with high steroids and during rapid corticosteroid withdrawal. Usually have substantial weight gain during steroid treatment. Firm subcutaneous nodules after month of tapering the steroids. Most cases resolve spontaneously, may need to restart steroids and taper more slowly. Histologically identical to subcutaneous fat necrosis of newborn. -----Traumatic Panniculitis: mostly on trunk and breasts of women. Anterolateral thigh from desk or chair may result in semicircular bands of atrophy called lipoatrophia semicircularis. Myospherulosis: subcutaneous cystic lesions induced by trauma with hemorrhage into areas of high lipid content. ------Facticial panniculitis: From injection. Special stains, electron microscope may be needed. --------Sclerosing Lipogranuloma: Granulomatous and fibrotic reaction from silicone or mineral oil injection. Topical antibacterial can occasionally cause. Months to years after exposure. Usual areas: penis, scrotum, breasts, nose, buttocks. Injected material can migrate locally and sometimes to lymphoreticular system and lungs leading to hepatosplenomegaly and pulmonary fibrosis. ---------Enzyme related: Pancreatic Panniculitis: From pancreatitis or pancreatic carcnimoa. Rarely from anatomic pancreas problems, hypertriglyceridemia, drug-enduced. 1. Epi: M:F 2:1 pancreatitis, 7:1 pancreatic CA. Mostly acinar cell. 40% of times skin cases first symptoms of pancreatic pathology. 2. Clinical: Tender or painless nodules 1-5cm in diameter. Lower leg 90%. Usually less than 10 lesions. Involve with scar, may break down and release oily material. a. Arthritis 54-88% of cases, monoarticular, oligoarticular. Usually in joints adjacent to panniculitis Joint fluid with FFA, suggesting from fat necrosis adjacent to joint space. Also can have medular fat necrosis of bone b. PE, pulmonary infiltrates

3. Amylase, lipase elevated. 60% with eosinophilia. 4. Histology: fat necrosis with ghost cells, some calcium, and dense inflammatory polymorphous infiltrate. EN on differential. 5. Treat panniculitis by removing cause. Alpha-1 antitrphysin: Most abundan antiprotease in circulation, potent and irrevesrible inactivator of neutrophil elastase. Hetezygous 1:50, homo 1:2500. 1. Clinical: Emphysema, liver disease. 2. PiZZ or PiSZ phenotypes get panniculitis 3. Panniculitis: Betwen 20-40, but can occur in childhoold. M=F. Lesions after minor trauma spontaneously. 4. Treatment: replacment of enzyme leads to resolution of skin lesions 5. Dapsone, doxycycline, colchicine. ----------Cytophagic histiocytic panniculitis (CHP): multisystem disease characterized by widespread erythematous painful sub Q nodules. Progresive febrile illness with hepatosplenomegaly, pancytopenia, hypertriglyceridemia, and liver dysfunction. Result from proliferation of histioytes. Spectrum of disease in children adn adults. Some triggered by viral EBV, HIV, other lymphoma. Histologically, infiltation of lobules of subcutaneous fat by histiocytes. Bean bag cells are histiocytes with phagocytized red blood cells. On spectrum of hemophagocytic sydnrome. Cyclosporine, corticosteroids, anakinra. Chemotherapy, BMT. ----------Gouty panniculitis: uric acid crystals deposited. -----------Lipodystrophy: Marked reduction in subcutaneous fat. Generalized/partial/localized, congenital or acquired. Congential (Berardinelli-Seip): Rare AR condition. 1. Clinical: Extreme paucity of fat in SQ tissues and other adipose tissues. Children with voracious appetitie, incrased height and heigh velocity, advanced bone age, muscular hypertrophy, and masculine habitus. Clitoromegaly possible. Scalp hair abundant and curly, hypertrichosis and hyperhidrosis. Acromegalic, acanthosis present. Get hyperinsulinemia, insulin resistance, and diabetes around puberty. a. Hypertriglyceridemia with eruptive xanthomas, pancreatitis. b. Lifespan shortened, die in young adulthood from DM, liver, or heart disease. 2. Genetics: AGPAT2, BSCL2, Caveolin-1 (Cav-1) 3. Treatment: if leptin low may benefit from replacement. Familial partial lipodystrophy: herteogenous AD group of patients. 1. Dunnigan type: Normal at birth, at puberty gradual loss of SubQ tissue in arms, legs, chest abdomen. Fat gain in face, neck, intra abdominal (cushinoid apperance). 2. DM, tryglyceridea, atherosclerosis.

3. Genetic defect: LMNA A &C. PPAR-gamma gene mutation: loss of SubQ tissue of forearms and calves. Diabetes, tryclycerides, HTN, hirsuitism. Mandibuloacral dysplasia: Hypoplasia of mandible and calvicle, acro-osteolysis, joint contrctures, mottled cutaneous pigmentation, skin atorphy, alopecia, bird-like facies, dental abnormality. Type A loss of fat from arms and legs, type B generalized. Acquired lipodystrophy: Most cases from HAART. 80% of HIV patietns with lipodystrophy. Related to NNRTI which inhibit yDNA polymerase of mitochrondria, leading to adipocyte apoptosis. Metformin and exercise reduces BMI and waist circumfrance. Trend towards treatment with TZDs. Growth hormone with short term improvement of visceral fat. Acquired partial lipodystrophy (Barraquer-Simons): 1. F:M 4:1, presents in first and second decades. Diffuse and progressive loss of sub Q fat that begins in face and scalp, progresses downward to iliac crests. Top half of body looks emaciated. 2. Sometimes associated with autoimmune disease. 3. Pathogenesis: Downregulartion of PPAR-y and adiponectin. Some with redced levels of C3 secondary to prsence of circulating polyclonanl IgG alled C3 nephritic factor that stabilizes C3 convertased and unopposed activation of alternative complement system, leading to excessive consumption of C3. Can lead to proteinuria from MPGN Acquired generalized lipodystorphy: Childhood or adolescence. F:M 3:1. Face, arms, legs, palms, soles, hepatic steatosis. Voracious appetitie. Acanthosis, cirrhosis in 20%, DM and hypertryglycerides may occur. 25% preceeding inflammatory panniculitis at onset. 25% with existing connective disease, especially juvenile dermato. Centrifugal abdominal lipodystrophy: from single region of Japan, childhood disease with depression of skin caused by loss of fat in groin or axillae, area enlarges then stops with pubety. After progression stops, skin returns to normal within a couple of years. Lipotrophia annularis (Ferreira-Marques): Affects women, usually involves upper extremitiy. Get depressed-atrophic bracelet-like constriction 1cm wide and up to 2cm in depth. Band persists for 20 years. Localized lipoatrophy: atrophy or hypertrophy may develop in women and children> men at sites of insulin injection.