JPC SYSTEMIC PATHOLOGY
Signalment (JPC #86N264D): A 6-year-old Shire gelding
HISTORY: This horse had a 1-month history of lameness and reluctance to move.
HISTOPATHOLOGIC DESCRIPTION: Hoof and 3rd phalanx: Diffusely the lamellar-horn margin is highly irregular and the normal architecture of the hoof wall is obscured by degeneration, necrosis, and marked irregular hyperplasia of the epidermal laminae. Diffusely, the primary epidermal laminae are markedly elongated and expanded up to four times normal by parakeratotic and orthokeratotic hyperkeratosis and occasionally contain accumulations of lamellated keratin or dyskeratotic keratinocytes. Secondary epidermal laminae are disorganized, blunted, clubbed, thickened or elongated and occasionally form anastomosing epidermal cords. Multifocally, there is loss of individual or groups of secondary epidermal laminae. Remaining epidermal laminar cells are often swollen with abundant pale, microvacuolated cytoplasm (intracellular edema) or separated by clear space (intercellular edema). In all layers of the epidermis, there are occasional scattered keratinocytes that have intensely eosinophilic cytoplasm and a pyknotic nucleus (necrosis). Multifocally, there are longitudinal clefts separating the epidermal laminae and basement membrane from the adjacent dermal laminae; clefts rarely contain a small amount of cellular debris and few erythrocytes. There are increased clear spaces separating fibrous connective tissue in both primary and secondary dermal laminae, and lymphatics within the laminar corium are frequently dilated (edema). Multifocally, the third phalanx exhibits scalloped margins lined by numerous osteoblasts with moderate numbers of osteoclasts within Howship’s lacunae and thin basophilic reversal lines that roughly parallel the surface (bony remodeling); P3 is multifocally capped by irregular proliferations of woven bone and the medullary cavity is filled with loose, myxomatous fibrous connective tissue. Caudal to P3 there is a nodular accumulation of degenerate neutrophils, macrophages, hemorrhage, finely fibrillar and beaded eosinophilic material (fibrin), and eosinophilic cellular and karyorrhectic debris (necrosis).
MORPHOLOGIC DIAGNOSIS: Hoof and 3rd phalanx: Epidermal laminar degeneration and necrosis, chronic, diffuse, severe with epidermal hyperplasia, hyperkeratosis, multifocal basement membrane retraction, edema, and bony remodeling of P3, Shire, equine.
- Laminitis is a common, painful condition of horses resulting in the separation of the epidermal laminae from the underlying basement membrane of the dermal laminae of the hoof
- Occurs in any hoofed species, especially horses & cattle
- Obese ponies are at increased risk
- Three histologic grades, which correspond to degree of lameness
- The pathogenesis of laminitis is not completely understood, and is likely multifactorial; the severe clinical signs are due to the separation of the distal phalanx (P3/coffin bone) from the inner hoof wall (rather than 1o inflammation)
- Current proposed mechanisms for the onset of laminitis: Inflammatory cytokines à Increase in Matrix Metalloproteinases-2 and -9 (MMP2, MMP 9) à Breakdown of epidermal laminae – elongation and disorganization of basal and parabasal keratinocytes, attenuation of tips of SEL and detachment of BM à Loss of BM àSeparation of dermal and epidermal laminae, which is key in loss of structural integrity of P3/hoof wall attachment. Collapse of secondary laminae à loss of capillaries à increased resistance to blood flow, arteriovenous shunting, and eventual ischemic damage.
- 3 Distinct forms of laminitis:
- Inflammatory laminitis: CHO overload, black walnut-induced, sepsis, systemic inflammation caused by GI disease, pneumonia, and septic metritis. Release of inflammatory toxins à degradation of BM and dyshesion of epithelial cells from BM, Matrix Metalloproteinase (MMP) activation, leukocyte infiltration, hemodynamic changes
- Endocrinopathic laminitis/laminopathy: Insulin resistance, obesity, pituitary pars intermedia dysfunction, hyperinsulinemia, +/- corticosteroid-induced; little if any inflammation, stretching of the secondary laminae rather than early separation from BM leading to eventual separation at the tips of the secondary epidermal laminae
- Contralateral limb laminitis/laminopathy: Initiated by poor blood flow/ischemia à enzyme activation and BM degradation + effects of increased load bearing (tension and stretch on lamellar tissues)
- Commonalities to all 3 forms: Dermal-epidermal separation at the interface of the lamellar basal epithelial cells and the underlying BM and dermis
- 3 phases of laminitis
- Acute: Increased hoof wall temperature, bounding digital pulse, severe pain, little gross alteration (no hoof deformity) but may have congestion/hemorrhage of laminar dermis and swelling above coronary band; may have acute separation/displacement of P3 (“sinker”)
- Chronic laminitis: Associated with rotational or vertical displacement of P3 relative to the hoof wall due to loss of interlocking force of epidermal laminae; if severely affected, P3 may penetrate the sole; the space between P3 and the hoof wall is filled with firm white tissue (proliferative epidermis), toe turns up, and cranial aspect of hoof has divergent horizontal ridges
TYPICAL CLINICAL FINDINGS:
- Pain, lameness, abnormal stance, reluctance to move
- Pounding digital pulses, increased temperature of hoof wall
TYPICAL GROSS FINDINGS:
- Acute: Swelling of coronary band
- Chronic: Circumferential divergent hoof rings, altered hoof growth, flattened sole, rotation +/- penetration of third phalanx through sole, depressed coronary band
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Secondary lamina lose their normal “club” shape and become elongated, tapered and disorganized with swelling, vacuolization and degeneration of secondary laminar epithelial cells
- Separation of secondary laminar epithelial cells from basement membrane, first in the region of parabasal cell attachment and later at basal cells (confirm with PAS), clumping of secondary laminar epithelial cells, loose aggregates of BM free within dermis
- Congestion, hemorrhage and edema
- Marked irregular hyperplasia and hyperkeratosis of the epidermal laminae
- Regenerated secondary laminae may have disrupted architecture and form anastomosing and irregular epidermal cords
- Remodeling of P3
- Shrinkage and loss of hemidesmosomes in basal epithelial cells
- Separation of basement membrane from epithelial cells
- Collapse of cytoskeleton tonofilaments
- Rounding of basal cell nuclei
ADDITIONAL DIAGNOSTIC TESTS:
- Radiography – determines rotation of P3 (a lack of parallelism on the lateral projection between the hoof wall and cranial face of the 3rd phalanx)
- Digital venograms and perfusion casts – decreased perfusion indicates a worse prognosis
- Magnetic resonance imaging
- Gross: Selenium toxicity results in hoof deformation and sloughing
- Laminitis can occur in all ungulates
- Pigs and ruminants: Laminar epidermis consists of primary laminae only
- There are several causes in cattle including chronic bovine besnoitiosis (Besnoitia besnoiti), carbohydrate overload, metritis, ketosis, mastitis, and a heritable form in Jersey
- Chronic cases may exhibit arteriosclerosis (unlike horses), chronic dermal granulation tissue, thrombosis, perineural fibrosis and perivascular accumulations of macrophages with hemosiderin and also parakeratotic hyperkeratosis
- Characteristic “slipper foot” with chronic recurrent bouts of subclinical laminitis.
- Cattle, Sheep, Pigs:
- Foot rot or hoof damage and secondary infection can result in laminitis in:
- Cattle and sheep: Bacteroides nodosus, Fusobacterium necrophorum
- Pigs: Fusobacterium necrophorum, Arcanobacterium pyogenes, Borrelia suilla
- Acute cases can also exhibit perineural edema and swelling of endothelial and smooth muscle cells of vessels
- The use of dirty, contaminated plunge baths leads to infection of skin abrasions, resulting in cellulitis and eventually laminitis; Erysipelothrix rhusiopathiae is most common
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- Eades SC. Overview of current laminitis research. Vet Clin North Am Equine Pract. 2010; 26(1):51-63.
- Engiles JB. Pathology of the distal phalanx in equine laminitis: More than just skin deep. Vet Clin North Am Equine Pract. 2010; 26(1):155-165.
- Engiles JB, Galantino-Homer HL, Boston R, McDonald D, Dishowitz M, Hankenson KD. Osteopathology in the equine distal phalanx associated with the development and progression of laminitis. Vet Pathol. 2015;52(5):928-44.
- Hargis AM, Ginn PE. The integument. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Mosby Elsevier; 2007; 1238-1239.
- Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC. Pathology of natural cases of equine endocrinopathic laminitis associated with hyperinsulinemia. Vet Pathol. 2015;52(5):945-56.
- Langenmayer MC, Gollnick NS, Majzoub-Altweck M, Scharr JC, Schares G, Hermanns W. Naturally acquired bovine besnoitiosis: Histological and immunohistochemical findings in acute, subacute, and chronic disease. Vet Pathol. 2015;52(3):476-88.
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