Cutaneous manifestations of amyloidosis: case of biphasic variant Vladyslava Doktor, DO, and Jay Dennett, DO St. John’s Episcopal Hospital, Far Rockaway, NY, Department of Dermatology Suzanne Sirota-Rozenberg, DO, Program Director Abstract Images Discussion Conclusion

The deposition of amyloid in the skin can occur as a skin- Amyloidosis is considered an abnormal deposition of This case is unique because it describes a patient with limited disorder or as a manifestation of systemic amyloid protein, which is made up of insoluble fibrils of rare variant of cutaneous amyloidosis without an obvious amyloidosis. In primary cutaneous amyloidosis, the beta-pleated sheets, in extracellular tissues. When it is cause. Patient’s subsequent diagnosis of diabetes deposits are derived from keratin intermediate filament directly deposited in the skin it is known as a primary mellitus type 2 draws parallels to endocrine connection proteins. The various forms include macular, lichen localized cutaneous amyloidosis. Table 2 lists different of amyloidosis production. nodular, biphasic and dyschromic amyloidosis. The types of localized amyloidosis. Biphasic amyloidosis, a causes range from friction induced, type 2 diabetes, rare variant, which signifies presence of concurrent A B Thorough history taking is of outermost importance. As in medullary carcinoma of thyroid, insulinoma to multiple lesions on macular and lichen amyloidosis. Literature an example of insulin-derived localized amyloidosis at an endocrine neoplasia type 2A. Systemic causes of describes several reports of biphasic amyloidosis in Asia injection site, it can cause poor glycemic control and cutaneous amyloidosis consists of plasma cell dyscrasia, and South America. However, no clear cause has been increase insulin dose requirements because of the chronic inflammatory disorder (e.g. rheumatoid arthritis), established to this date. It has been suggested that impairment in insulin absorption. autoinflammatory disorders (e.g. familial Mediterranean chronic friction, scratching and rubbing, for instance with When evaluating cutaneous amyloidosis, some mimickers fever) and chronic infections. towels, can cause several types of cutaneous might come in mind. Table 1 lists some of the more amyloidosis. Amyloid deposition in macular amyloidosis common lesions that can present as either macular or Our case describes a 33 year old female with no past and lichen amyloidosis is primarily caused by epidermal lichen amyloidosis. medical history who presented to our clinic with pruritic keratinocyte degeneration. Cytokeratin released from Our case illustrates the importance of increased mixture of reticulated and papular thin plaques on upper C D apoptotic basal keratinocytes is covered with awareness of cutaneous manifestations of amyloidosis back and lower extremities. D autoantibodies, phagocytosed by macrophages, and and the need for future research to elucidate any further enzymatically degraded to form amyloid. Patients with connections. The rarity of biphasic amyloidosis and its association with Figure A: reticulated hyperpigmented small plaques on the back. diabetes mellitus who inject insulin at the same site can diabetes mellitus makes this case of interest. Our case Figure B: dome-shaped papule coalescing into a rippled plaque on b/l shins before treatment. also develop localized insulin-derived amyloidosis at the emphasizes the importance of prompt diagnosis of Figure C: b/l shins after treatment. injection site. cutaneous amyloidosis. This will lead to timely treatment Figure D: pathology of macular amyloidosis- upper back (amyloid of any possible associated systemic disease. deposits in papillary dermis). Our patient, however, lacked history of physical rubbing References or any systemic illnesses at initial presentation. As it was discovered after thorough testing, patient had diabetes Case Presentation Black MM. The role of epidermis in the histopathogenesis of lichen amyloidosus. Br J Dermatol Differential Diagnoses mellitus. Recent studies have found that degeneration of 1971; 85: 524-30. pancreatic islet cells that is found in diabetes mellitus is Cooper, GJS, et al. Is type 2 diabetes amyloidosis and does it really matter to patients? also associated with islet amyloidosis. Perhaps this plays Diabetologia 2010 June;53(6):1011-1016. importance in our patient and offers a plausible Groves, R. (2018). Amyloidosis. In Bolognia, J and Schaeffer, J (4th Ed), Dermatology. (pp. A 33 year old female with no past medical history Table 1 754-762), Philadelphia. Elsevier Saunders. presented to clinic with pruritic mixture of reticulated and Macular Amyloidosis DDx: explanation on the origins of cutaneous presentation. Endocrine connection has also been established between Hernandez-Nunez, A, et.al. Widespread biphasic amyloidosis: response to acitretin. Clin Exp papule thin plaques to upper back (Fig. A) scapular Notalgia Paresthetica Dermatol 2001; 26: 256–9. region) and bilateral shins (Fig. B) of three years Tinea Versicolor local amyloidosis and Multiple Endocrine Neoplasia Confluent and reticulated papillomatosis Jih, M. Biphasic cutaneous amyloidosis. Dermatol Online J. 2001 Dec;7(2):15. duration. Patient denied any inciting events prior to rash Type 2, a group of endocrine disorders. More specifically, Drug-induced hyper pigmentation medullary thyroid carcinoma is associated with amyloid Kalkan, G, et al. An alternative treatment model: the combination therapy of narrow band appearance. However, patient did complain of mild Erythema Dyschromicum Persians ultraviolet B phototherapy and tacrolimus ointment 0.1% in biphasic amyloidosis. J Pak Med production. Assoc. 2014 May;64(5):579-82. pruritus on lower extremities. After a through history, Actinic lichen planus physical exam and biopsy of the upper back (Fig. D), the Katzman, BD, et al. New histologic findings of amyloid insulin bodies at an insulin injection site in a patient with diabetes. Am J Dermatopathol 2017;0:1-4. patient was diagnosed with biphasic amyloidosis. This is Lichen Amyloidosis DDx: Treatment Wolfgang W, Imke W, Matthias B, Carlos DC. Lichen Amyloidosus. A consequence of scratching. consistent with biopsy proven macular amyloidosis on the Lichen Simplex chronics J Am Acad Dermatol 1997; 37: 923-8. back and clinically diagnosed lichen amyloidosis on the Prurigo Nodularis There are some anecdotal cases of various treatment legs. The patient was subsequently tested to rule out Hypetrophic Lichen Planus options. One case of 73-year-old man with a 15-year Localized lichen myxedematosus possible systemic causes blood work including CBC, history of biphasic amyloidosis was treated with acitretin Pretibial myxedema 35 mg once daily dose (0.5 mg/kg/day) for 6 months with CMP, thyroid and renal function tests, HgA1C, ESR and Elephantitis nostras verrucosa hepatitis panel. All but one test were within normal limits success. Another recalcitrant case of 26-year-old woman Table 2: Clinical classification of amyloidosis (HgA1C was 6.7). with a 7-year history of biphasic amyloidosis was treated Organ-limited (localized) amyloidosis with topical tacrolimus ointment 0.1% and narrow band Cutaneous On further questioning, patient admitted to familial history ultraviolet B treatment simultaneously for 8 weeks. At that •Primary: macular, lichen, biphasic, dyschromic, nodular point significant improvement was noticed, however, the of diabetes mellitus (i.e. both parents). Patient was •Secondary: incidental finding within various skin tumors treated with topical corticosteroid therapy to ameliorate (e.g. dermatofibroma, intradermal melanocytic nevi, patient had moved away from the treatment center and pruritus for 3 weeks. Subsequently, patient reported seborrhea keratoses, adnexal tumors, basal cell could not continue with the treatment any longer. More improvement not only in pruritic symptoms but also in carcinoma, Bowen disease, porokeratosis); following PUVA common therapeutic options include antihistamines, texture and color of lower extremities (Fig. C). Patient therapy potent topical cortricosteroids, keratolytic agents, Endocrine was also advised to follow up with primary care physician intralesional corticosteroids, and capsaicin. It is certainly •Medullary carcinoma of the thyroid, insulinoma, type 2 for treatment of her newly diagnosis diabetes mellitus. important to hold a discussion on avoidance of diabetes aggravating factors such as itching or rubbing the Cerebral affected area. •Alzheimer disease