Worseninginduratedpinktranslucentnodulesandseverehyperkeratosisofthelowerextremi9es:ACaseofElephan9asicPre9bialMyxedema.
JasonSolway,DO,ObenOjong,DO,JohnMoesch,DO,MichaelR.Heaphy,Jr,MD,Ma;hewMahoney,MD.Largo Medical Center, Largo, Florida
LEARNING OBJECTIVES FIGURES • Recognizingelephan9asispre9bialmyxedema(PTM)• Understandingpathophysiologyofelephan9asisPTM.• Crea9ngtreatmentplanforpa9entsufferingfrom
elephan9asisPTM.• Ddxforelephan9asisPTM.
CASE PRESENTATION • HPI:A61yearoldwhitewomanpresentedwithbilateral
lowerextremityderma99s,swellingandskinthickeningthatbegan5yearsago;shortlybeforeshewasdiagnosedwithGravesdisease(Figures1-3).
• Pa9ent’ssymptomsprogressivelyworsenedpost
thyroidectomyandachievementofeuthyroidstatewithlevothyroxine.Previousdiagnosesincludedcelluli9sandlymphedematreatedwithmul9plefailedaVemptsoforalan9bio9cs.Nofamilyhistoryofrelatedcondi9ons.Nopreviousbiopsywasobtained.
• PHYSICALEXAM:Indurated,1-2cmthickviolaceous
plaqueswithinterspersedpinktranslucentnodules;associateddeepfissureswithac9veserousdrainageandoverlyingyellow-whitecrustonbilateralpre9bialareas,anklesanddorsalfeet.(Figures1-3)Plantarsurfacewascoveredbythickscale.
• Otherphysicalexamfindingsincludedproptosis,exophthalmosandsurgicalscarontheanteriorneck.
• DX:A`erobtaininginformedconsent2biopsyspecimens
wereobtainedforhematoxyllin-eosinandotherspecialstains(Figures3-6).
• Elephan9asispre9bialmyxedemawasdiagnosedbasedontheseclinicalandhistologicalfindings.
DISCUSSION
1 2 3
54 6
Figures 1-3: Clinical images of indurated 1-2cm thick violaceoous plaques with interspersed pink translucent nodules; associated deep fissuring and non pitting edema. Figure 3: Active serous drainage with overlying yellow-white crust on pretibial area.
Figures 4-5: H&E of a 6mm punch biospy on the right shin and right dorsal foot. Hyperkeratosis,papillomatosis,andacanthosisoftheepidermis.Largequan99esofmucinaredepositedwithinthere9culardermis,causingcollagenbundlestoseparateandthedermistothicken.Agrenzzoneofnormalcollagenisalsoobserved.Figure 6: Colloidal iron stain demonstrating an abundance of mucin in the throughout the dermis.
REFERENCES
• EPIDEMIOLOGY: Elephantiasic pretibial myxedema (PTM) is the most severe variant of non-filarial myxedema occurring in only 1% of patients with Grave’s disease1.
• PATHOPHYSIOLOGY: It is theorized that T-cells stimulate shared antigens between the thyroid and pretibial tissue and release TGF-B and IL1-alpha that stimulate fibroblasts to produce and deposit mucin-like glycosaminoglycans in tissue. The pretibial fibroblasts may be more sensitive to this stimulation2.
• The Pretibial area is favored secondary to hydrostatic forces, decreased lymphatic cytokine clearance and dependent position3.
• CLIINICAL: Grossly enlarged and disfigured appendage, usually with functional restriction and cosmetic concerns for the patient. Cutaneous changes include non-pitting edema of lower extremities that does not resolve with elevation. The initial cobblestone appearance later becomes mossy and verrucous. Because hair follicles are prominent, it produces the characteristic peau d’orange appearance 3,6.
• Ulceration and bacterial seeding with recurrent cellulitis or fungal infections are common, with patients complaining of pain or pruritus6.
• PATHOLOGY:Large amounts of mucinous deposition are seen in the reticular dermis. There is a lack of angioplasia and hemosiderin. Sparse lymphocytic deposition in perivascular spaces and moderately increased mast cell deposition are seen3.
• The number of collagen fibers is reduced with increased edema, and occasional acanthosis, hyperkeratosis, and papilomatosis 4-5.
• TREATMENT: Cosmesis and restoration of function are the primary aims in ENV treatment3.
• Therapeutic modalities like complete decompressive physiotherapy, topical corticosteroids with occlusive dressing, psoriatane, octreotide and weight reduction have proven beneficial7.
• Tobacco cessation is imperative as it has been linked to autoimmune manifestations of Grave’s disease7.
1. Humbert P, Dupond JL, Carbillet JP. Pretibial myxedema: an overlapping clinical manifestation of autoimmune thyroid disease. Am J Med. 1987;83:1170-1171.
2. Korducki JM, Loftus SJ, Bahn RS. Stimulation of glycosaminoglycan production acids in localized in cultured human retroocular fibroblasts. Invest Ophthalmol Vis Sci 1992 59 (3): 409-16 May; 33 (6): 2037-42
3. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. American Journal of Clinical Dermatology. 2005 6(5):295-309.
4. Schwartz KM, Fatourechi V, Ahmed DD, et al. Dermopathy of Graves’ disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab 2002 Feb; 87 (2): 438-46.
5. Sanders LJ, Slomsky JM, Burger-Caplan C. Elephantiasis nostras: an eight-year observation of progressive nonfilarial elephantiasis of the lower extremity. Cutis. 1988 Nov; 42(5):406-11.
6. Ruocco E, Puca RV, Brunetti G, Schwartz RA, Ruocco V. Lymphedematous areas: privileged sites for tumors, infections, and immune disorders. Int J Dermatol. 2007 Jun; 46(6):662.
7. Susser WS, Heermans AG, Chapman MS, et al. Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder. J Am Acad Dermatol 2002 (May); 46 (5): 723-726.
