Sec 10 Disorders of Subcutaneous Tissue Flashcards
Occurs in both genders, at any age from childhood to 70 years of age, but is more common in young women in the 2nd-4th decades of life; considered to be a hypersensitivity reaction presents as an acute onset of tender, painful, erythematous, warm nodules and plaques on the anterior and at times the lateral aspect of both lower legs and ankles lasts from 3 to 6 weeks
Erythema nodosum
The nodules of EN may persist a few days or weeks, may become confluent, and evolve from an erythematous or purple-like hue to a bruise-like pigmentation called
Erythema contusiforme
Histopathology: widened septa with inflammatory infiltrate including multinucleated giant cells; may have Miescher’s granulomas which shows a discrete micronodular aggregate of small histiocytes around a central stellate cleft
Erythema nodosum
Treatment: Erythema nodosum
Treatment or removal of the etiologic factor
An inflammatory panniculitis, most commonly presenting with ulcerated nodules on the calves, and frequently associated with MTB infection
Erythema induratum
A similar disorder to EI, without ulceration appearing in calves and other lower extremity sites was subsequently described without MTB association
Nodular vasculitis
Seen most commonly in young to middle-aged women, presenting as recurrent erythematous to violaceous nodules and deep plaques on the lower legs that may be tender; may heal without scarring, but often ulceration leads to scarring; can have a protracted course with recurrent episodes over years and for the most part, patients are in fairly good health
Erythema induratum/Nodular vasculitis
Histopathology: shows a mostly lobular panniculitis with extensive adipocyte necrosis and vascular damage-necrotizing vasculitis of small venules in the fat lobule.
Erythema induratum/Nodular vasculitis
Treatment: Erythema induratum
Treatment with triple agent antituberculosis therapy
Most common form of panniculitis, occurs in association with venous insufficiency, mostly in overweight women
Lipodermatosclerosis
Pathogenetic factors in LDS
Elevated hydrostatic pressure-induced increased vascular permeability secondary to down-regulation of tight junctions with extravascular diffusion of fibrin
Microthrombi
Abnormalities in protein S and protein C
Hypoxia
Damage to endothelial cells by inflammatory cells
Upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), leukocyte function-associated antigen 1 (LFA-1), platelet- and endothelial-derived factors
Inflammation with wound healing and local collagen stimulation leading to fibrosis and further vascular and lymphatic damage
Presents with very painful, poorly demarcated, cellulitis-like erythematous plaques to purple somewhat edematous indurated plaques or nodules on the lower legs, most commonly on the lower anteromedial calf area; scaling may be present; pain can be so intense; may last a few months or even a year
Acute form of LDS
Presents with indurated to sclerotic, depressed, hyperpigmented skin on the lower portion of the lower leg, predominantly but not limited to the medial aspect, or in a stocking distribution; described as having an “inverted champagne bottle” or a “bowling pin” appearance
Chronic form of LDS
Biopsy for Liposermatosclerosis if warranted
A thin elliptical excision from the margin of an erythematous and indurated area, closed primarily with sutures
Histopathology: Dermal stasis changes are present at any stage, early lesions show a sparse infiltrate of lymphocytes in the septa, accompanied by central lobular ischemic fat necrosis recognized by the presence of pale-staining, small anucleate adipocytes. Capillary congestion is also observed within fat lobule.
Lipodermatosclerosis
The major universally recommended treatment for LDS
Compression therapy
30–40 mm Hg - more effective
15–20 mm Hg or 20–30 mm Hg - higher rate of compliance
Panniculitis directly caused by an infectious agent which can be due to bacteria, mycobacteria, fungi, protozoa, and viruses.
Infection-induced Panniculitis
Clinical appearance varies from fluctuant- or abscess-type lesions with purulent discharge and ulcerations to nonspecific erythematous firm nonfluctuant subcutaneous plaques and nodules, purpuric plaques, and EN-type lesions. The most common sites are the legs and feet. Immunosuppression is associated with more widespread abscess-type lesions.
Infection-induced Panniculitis
Histopathology: the subcutaneous fat contains a dense infiltrate of neutrophils and some admixed lymphocytes and macrophages, often with extension into the overlying dermis and with abscess formation a common finding. Other features include hemorrhage, vascular proliferation, foci of basophilic necrosis, and sweat gland necrosis.
Infection-induced Panniculitis
Most commonly associated with pulmonary and hepatic disease, leading to chronic obstructive pulmonary disease (COPD), hepatic cirrhosis, or hepatocellular carcinoma; the ZZ genotype is at highest risk.
α1 Antitripsin deficiency
Patients present with painful erythematous nodules and plaques, but early lesions may have a cellulitic or fluctuant abscess-type appearance. Lesions may ulcerate and discharge an oily material or serosanguineous discharge and resolve with atrophic scars. The lesions appear most commonly on the lower trunk (buttocks) and proximal extremities. Trauma or excessive activity may precede the onset of lesions.
α1 Antitripsin Deficiency Panniculitis
Histopathology: Early lesions may reveal edema and degeneration of adipocytes, with ruptured and collapsed cell membranes and a perivascular mononuclear infiltrate; splaying of neutrophils between collagen bundles throughout the overlying reticular dermis, considered an early and distinctive diagnostic clue. More advanced lesions have masses of neutrophils and histiocytes associated with necrosis and replacement of fat lobules. A focal pattern of involvement is another distinguishing feature with large areas of normal fat in immediate proximity to necrotic septa and fat lobules.
α1 Antitripsin Deficiency Panniculitis
Due to release of pancreatic enzymes such as lipase, amylase, and trypsin into the circulation, promoting vascular permeability, leading to release of fatty acids from adipocytes and subsequent fat necrosis.
Pancreatic panniculitis
Presents with lesions appearing most frequently on the lower legs, especially the periarticular areas. Lesions often appear in crops, ill-defined erythematous to red–brown edematous tender nodules, which in mild cases may involute and resolve with atrophic hyperpigmented scars, may have central “softer” areas or may become fluctuant, abscess-like, and drain oily material.
Pancreatic panniculitis
Histopathology: demonstrate lobular fat necrosis with distinctive qualities. Adipocytes lose their nuclei but maintain peripheral outlines, forming characteristic “ghost cells”. With saponification, calcification occurs, producing fine granular basophilic deposits within and around individual necrotic adipocytes.
Pancreatic panniculitis
Rare variant of lupus erythematosus (LE), which primarily affects the subcutaneous AT presents with tender and painful and usually appear on the upper arms (lateral aspect), shoulders, face, scalp, hips, buttocks, breasts, and rarely on the lower extremities. The lesions are deep subcutaneous nodules with or without any surface changes.
Lupus Erythematosus Panniculitis
Histopathology: vacuolar alteration of the basal cell layer, thickened basement membrane, mucin deposition between dermal collagen bundles, and a superficial and deep perivascular inflammatory infiltrate of lymphocytes. The AT shows a mostly lobular or mixed lobular and septal panniculitis, with lymphocytes, often with formation of lymphoid follicles.
Lupus Erythematosus Panniculitis
First line treatment for Lupus Erythematosus Panniculitis
Antimalarials (Hydroxychloroquine + Quinacrine)
Presents as painful indurated erythematous nodules and plaques on the arms, buttocks, thighs, and abdomen; these may ulcerate and result in lipoatrophy. The nodules and plaques usually present in association with the characteristic cutaneous manifestations.
Panniculitis in association with Dermatomyositis
Histopathology: mostly lobular panniculitis, or mixed lobular and septal panniculitis, with lymphocytic and plasma cell infiltrates, hyaline sclerosis and fibrosis of septal collagen bundles, progressive replacement of the fat by fibrosis, and calcification (25%).
Panniculitis in association with Dermatomyositis
Rare panniculitis that occurs in the first few weeks of life. Lesions are sharply demarcated, erythematous to violaceous, firm, indurated nodules, or plaques located on the back, shoulders, arms, buttocks, thighs, or face, but usually not on the anterior trunk.
Subcutaneous Fat Necrosis of Newborn
Histopathology: mostly lobular panniculitis with focal necrosis of the fat lobule and a dense inflammatory infiltrate of lymphocytes, histiocytes, and foreign body giant cells; a few eosinophils may insinuate between the fat cells. Many adipocytes retain their cellular outlines, but contain fine eosinophilic strands and granules as well as needle-shaped clefts in radial array.
Subcutaneous Fat Necrosis of Newborn
Presents with circumscribed, red to violaceous, subcutaneous nodules or plaques on the face and thighs, and rarely of the scrotal fat in prepubertal boys. Follows exposure to cold weather, popsicles, ice packs, and swimming in cold ocean water.
Cold Panniculitis
Histopathology: lobular panniculitis (lymphohistiocytic or mixed infiltrate) without vasculitis. Perivascular lymphohistiocytic infiltrate involving blood vessels at dermosubcutaneous junction and within overlying dermis.
Cold Panniculitis
Reaction in AT induced by external factors, usually injection of foreign materials or any means of trauma. lesions present a spectrum of clinical findings, from papules and nodules to erosions or ulcerations with perfect round or angulated appearance.
Factitial Panniculitis
Heterogeneous group of disorders characterized by selective loss of adipose tissue.
Lipodystrophies
The extent of fat loss only in small areas
Localized lipodystrophy
The extent of fat loss is more extensive fat loss, involving the extremities
Partial lipodystrophy
The extent of fat loss involved entire body
Generalized lipodystrophy
Most common lipodystrophy, AD
Familial partial lipodystrophy of Dunnigan variety
Can be recognized at birth or soon thereafter due to near total loss of body fat, marked muscularity, prominent subcutaneous veins, acromegaloid features, acanthosis nigricans, hepatomegaly, and umbilical prominence or hernia.
Congenital generalized lipodystrophy
Autosomal dominant disorder characterized by fat loss from the limbs with variable fat loss from the trunk and increased sc fat deposition in nonlipodystrophic regions. Has normal body fat distribution during early childhood, but around the time of puberty, subcutaneous fat from the extremities and trunk is progressively lost.
Familial Partial Lipodystrophy
Have characteristic skeletal abnormalities including hypoplasia of the mandible and clavicles, acroosteolysis, cutaneous atrophy, progeroid features such as thin beaked nose, hair loss, thin skin with prominent superficial vasculature and mottled hyperpigmentation, delayed dentition and closure of cranial sutures, joint stiffness, and lipodystrophy. Those with ZMPSTE24 mutations develop clinical manifestations earlier in life, are premature at birth, and can develop focal segmental glomerulosclerosis and calcified skin nodules.
Mandibuloacral Dysplasia
SHORT Syndrome
Short stature Hyperextensibility or inguinal hernia Ocular depression Rieger anomaly Teething delay
Presents as a spectrum of clinical manifestations ranging from onset during the first months of life to later during childhood. Early features are recurrent fevers, annular violaceous plaques, poor weight and height gain, persistent violaceous eyelid swelling, hepatomegaly, arthralgias variable muscle atrophy, and progressive lipodystrophy. Histopathologic examination of lesional skin shows atypical mononuclear infiltrates of myeloid lineage and mature neutrophils, and laboratory abnormalities include chronic anemia, elevated acute-phase reactants, and raised liver enzymes with a cytokine profile showing high levels of IP-1, MCP-1, IL-6, and IL-1Ra, consistent with an IFN signaling signature.
CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature)
The autosomal recessive, syndrome presents with generalized loss of body fat and muscle mass and progeroid appearance at birth.
Neonatal progeroid (Weidemann–Rautenstrauch) syndrome
Develops in most patients before age 15. Patients lose subcutaneous fat gradually in a symmetric fashion starting with the face and then spreading downwards. Most of them present with fat loss from the face, neck, upper extremities, and trunk with sparing of sc abdominal fat and lower extremities. Approximately, 20% of the patients develop mesangiocapillary (membranoproliferative) glomerulonephritis, and some develop drusen. No metabolic complications.
Acquired partial lipodystrophy (Barraquer-Simons Syndrome)
Present with variable amount of sc fat loss usually during childhood. Although many patients have generalized loss of fat, some areas are spared usually, intra-abdominal or bone marrow fat. However, patients develop extremely severe hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia.
Acquired generalized lipodystrophy (Lawrence Syndrome)
Patients usually lose sc fat from the face, trunk, and extremities 2 years or more after receiving PI-containing HAART. Fat loss from the face can be so severe as to result in an emaciated appearance. Some of them develop buffalo hump, double chin, and also gain intra-abdominal fat. The fat loss progressively gets worse with ongoing HAART therapy and does not reverse on discontinuation of PIs.
Highly Active Antiretroviral Therapy-Induced Lipodystrophy in Human Immunodeficiency Virus-Infected Patients
Most common cutaneous lesion seen in patients with lipodystrophy
Acanthosis nigricans
Mainstay of treatment of Lipodystrophy
Cosmetic surgery
Management of complications
