Primary localized cutaneous amyloidosis − a review : Pigment International

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Primary localized cutaneous amyloidosis − a review

Somani, Vijay K.; Somani, Anirudh; Sarkar, Rashmi

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Pigment International 10(1):p 4-13, Jan–Apr 2023. | DOI: 10.4103/pigmentinternational.pigmentinternational_
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Amyloidosis can be classified as systemic with involvement of various organ systems and localized in which deposits are limited to a single organ. Dermatologists likely encounter amyloidosis as a primary cutaneous form or rarely as cutaneous manifestations seen in systemic forms. Primary localized cutaneous amyloidosis refers to a group of conditions characterized by deposition of extracellular homogenous hyaline material in the skin, particularly, the papillary dermis, without any systemic involvement.[1] Lichen amyloidosis, macular amyloidosis, and nodular amyloidosis are different subtypes of primary localized cutaneous amyloidosis (PLCA).

The condition can present as a relatively innocuous skin disfigurement on one hand and a progressive life-threatening systemic disease with multiorgan involvement on the other hand.


Rudolf Virchow first introduced the term amyloid in 1854, after observing that amyloid behaved like starch after staining with iodine. Gutmann first described the clinical features of lichen amyloidosis and named the disease, “amyloidosis cutis nodularis et disseminate.” “Lichen amyloidosis” was coined by Freudenthal in 1930.[2,3]

Macular form of cutaneous amyloidosis was first described by Palitz and Peck in 1952.[4]


The primary localized cutaneous amyloidosis is prevalent worldwide. Majority of cases are sporadic, but about 10% of cases have been reported to be familial.[1,5]

It is quite common in Southeast Asian countries, China, and South America.[6,7] Macular and Lichen amyloidosis are seen more frequently in skin types III and IV with a female preponderance. The age of onset ranges between 21 and 50 years.[8]


Amyloidosis is broadly classified into two types, systemic and cutaneous [Table 1]. The source of amyloid in cutaneous form is generally near the affected site, whereas it is secreted in the blood and deposited in various organs in systemic type.

Table 1:
Clinical classification of amyloidosis.



Amyloid is comprised of three components. Major component is the amyloid fibrils, a loose network of unbranched fibrils, about 10 to 15 nm in diameter. The fibrillar protein determines the type of amyloid and the associated systemic disease.[9] Important ones include AL (immunoglobulin light chain) responsible for primary systemic amyloidosis, type AA (serum amyloid A) implicated in secondary systemic amyloidosis and type ATTR (transthyretin) causing familial amyloidotic polyneuropathy.[10] Second non-fibrillar component is amyloid P, identical to serum amyloid protein (SAP) constituting about 15% of amyloid deposits and the third component is the ground substance comprised of glycosaminoglycans and apoE lipoprotein mainly.

Precise pathogenesis of PLCA has not been elucidated fully, but various factors like genetic predisposition,[11] friction,[12,13,14] sunlight,[14] atopy,[15] and Epstein Barr virus[16,17] have been implicated. Amyloid in macular and lichenoid variants is derived from keratinocytes, as they are positive for cytokeratin K5.[18] Two pathogenic mechanisms have been proposed, regarding the origin of amyloid in PLCA. The fibrillar theory proposes that the tonofilaments of apoptotic keratinocytes undergo filamentous degeneration and are deposited into the dermis. These are phagocytosed by histiocytes and fibroblasts and modified into amyloid material.[18] According to the secretory theory, degenerated basal keratinocytes secrete amyloid material which then drops into the dermis through damaged lamina densa.[19] The amyloid in nodular amyloidosis is derived from plasma cells, because it is composed of immunoglobulin light chains (in contrast to cytokeratins seen in MA and LA), similar to the systemic forms of amyloidosis.[18,20]

Primary localized cutaneous amyloidosis

In primary localized cutaneous amyloidosis, amyloid deposits are seen in previously normal skin, with no evidence of deposits in internal organs.[1] More common macular and lichen amyloidosis share same pathogenic mechanisms.[18]

Pathogenic mutations in the oncostatin M receptor (OSMR) gene and interleukin-31 receptor A (IL-31RA) are believed to be the major cause for familial type of PLCA.[21,22] Higher frequency of OSMR mutation was reported in sporadic type of PLCA also. Higher mutation rates in OSMR genes were observed in familial type of PLCA and in female patients, when compared to male patients of PLCA.[23,24]

Friction or oft repeated trauma by towels, nylon scrubbers, and clothes has been implicated in the causation of MA, and is described as friction amyloidosis or nylon friction dermatitis.[12,25,26]

Frequent involvement of sun-exposed areas, and exacerbation of the melanosis on exposure to sunlight could point to sunlight as one of the possible contributory factors in PLCA.[14] Other risk factors implicated in the etiology include female gender,[27,28,29] atopy,[15] and race.[30] Its predilection among certain races, the familial occurrence in about 10% and its association with multiple endocrine neoplasia type 2A points to genetic susceptibility in the etiology.[31,32]

PLCA has been described in associations with various immune disorders that include: systemic sclerosis,[33,34,35,36] CREST syndrome,[37] rheumatoid arthritis,[38] systemic lupus erythematosus,[38,39] primary biliary cirrhosis,[40] autoimmune cholangitis,[41] Kimura’s disease,[42,43] ankylosing spondylitis, and autoimmune thyroiditis.[44] IgA nephropathy and sarcoidosis were also reported to be associated with PLCA, and it was proposed that atypical and extensive PLCA in association with immune disorders could be a subset of cutaneous amyloidosis, thus supporting immune dysregulation as a cause in PLCA.[45]

Three types of PLCA are described.

Macular amyloidosis (MA) 35%

Lichen amyloidosis (LA) 35%, and

Nodular amyloidosis

Biphasic amyloidosis (15%) describes the presence of both the macular and papular variants in the same patient.[46]

Clinical features

Macular amyloidosis

Macular amyloidosis usually presents in adults and comprises of about 1/3rd cases of PCLA. It clinically presents as small, brownish macules with a characteristic reticulated or rippled pattern, which may coalesce to form poorly circumscribed hyperpigmented areas.[29] The most common site of involvement is the upper back, especially the interscapular area [Figure 1]. Extensor surfaces of the extremities [Figure 2], like forearm and shin, are involved quite frequently.[27,29,47] Face, neck, breast, and areas adjacent to bony prominences also may be involved, especially when nylon scrubbers are used while bathing.[12] Anosacral amyloidosis has been described in Japanese and Chinese patients. Amyloidosis of the auricular concha[48] and temple area has been described.[49] It occurs more frequently in women and generally has an earlier age of onset.[8,50]

Figure 1:
Typical involvement of the interscapular area in macular amyloidosis.
Figure 2:
Macular amyloidosis involving the extensor Legs.

Histopathologically, mild epidermal hyperkeratosis is sometimes seen. Irregularly scattered eosinophilic amyloid globules can be visualized in papillary dermis. Melanophages occasionally are seen in the periphery of these deposits [Figure 3].[51]

Figure 3:
Macular amyloidosis − basket-weave orthokeratosis, basal hyperpigmentation, pigment incontinence, and amyloid deposits in the upper dermis. Congo red staining (×100).

Patients seek medical attention for pigmentation and the troublesome pruritus. Pruritus ranges from mild to moderate and may be absent in about 20% of cases.[27]

Though the rippled and reticulate pattern is the most common presentation, many unusual forms, like poikilodermatous,[52,53,54] diffuse,[55] bullous,[56] nevoid,[57] linear,[58] amyloidosis cutis dyschromica,[59] incontinentia pigmenti like,[60] are reported.

Lichen amyloidosis (LA)

It accounts for about 35% cases of primary cutaneous amyloidosis.[7] It is seen more frequently in men and manifests at a later age, around 5th or 6th decade. Sites most often involved are the shins and extensor forearms [Figure 4]. It can involve upper back and thighs less frequently.[61] Initial lesions are discrete, intensely pruritic, firm, hyperkeratotic papules, arranged in linear or grouped pattern. They may coalesce later to form hyperpigmented rough plaques. Pruritus is intense and Koebner’s phenomenon may be seen.[62,63] The constant itching and scratching are believed to induce LA.[64] Cutaneous small-fiber neuropathy and hyper-responsiveness, and over expression of IL-31 receptors in the skin is thought to be the reason for pruritus in it.[65]

Figure 4:
Lichen amyloidosis involving the shins.

Histologically, epidermis shows acanthosis, papillomatosis, and hyperkeratosis. Rete ridges are elongated [Figure 5].[51] Basal keratinocytes may show hyperpigmentation and vacuolar degeneration. Large globular deposits of eosinophilic amyloid in papillary dermis are noted. Melanophages outside the deposits are seen more frequently than in MA.[66,67,68]

Figure 5:
Lichen amyloidosis − compact orthohyperkeratosis, acanthosis, and amorphous amyloid deposits with melanin granules in the dermal papillae H&E ×400.

Lichen amyloidosis may be associated with multiple endocrine neoplasia type 2A, primary biliary cirrhosis, systemic lupus erythematosus, and Sjogren syndrome.

Both the variants, macular and lichen have a protracted course, and have not been reported to progress to systemic amyloidosis.

Dermoscopic features

The most common dermoscopic finding of MA was a central hub, which could be either white or brown, surrounded by various configurations of pigmentation, including fine streaks, leaf-like extensions, and a noncircular thick pedal projection with a smooth border [Figure 6].[51]

Figure 6:
Dermoscopic picture of macular amyloidosis − venation like extension of pigmentation from white central hub.

The central hub in LA was found to be either white or scar-like surrounded by brownish dots or a rim of white collarette [Figure 7].[51]

Figure 7:
Dermoscopic picture of lichen amyloidosis − whitish scar-like center surrounded by some brownish dots (arrows) or a rim of white collaret (arrowhead).

Nodular amyloidosis (NA)

Nodular amyloidosis is very rare and the source of amyloid is believed to be local plasma cells. The precursor protein in NA is Amyloid L, in contrast to K5 cytokeratin associated with MA and LA. Nodular amyloidosis presents as a single or multiple waxy nodules or infiltrated plaques on the face, trunk, and usually extremities.[69,70,71] About 25% of cases have been reported to be associated with Sjogren syndrome leading to speculation of a shared pathogenesis between these two conditions.[72,73,74,75,76]

Other autoimmune disorders reported to be associated with NA include primary biliary cirrhosis, rheumatoid arthritis, systemic lupus erythematosus, and CREST syndrome.[77] The cause of NA is not known but some patients give a history of preceding trauma.[78,79,80]

In nodular amyloidosis, amyloid is not limited to the papillary dermis but is present in the entire dermis, and seen even extending into the subcutaneous fat and also involves the blood vessels. A perivascular infiltrate of plasma cells[81] contiguous to the deposits implies local synthesis of amyloid L, the precursor protein of NA.

NA, though considered a localized clonal plasma cell disorder is known to progress to systemic amyloidosis. Northcutt and Vanover[71] estimated the rate of progression to be 15%, after studying a cohort of 47 PLCA patients. Therefore, a long-term follow-up in patients with NA is advisable.

Dermoscopic features

It shows a distinct pattern from MA or LA. The features include linear and serpentine vessels over an orange-yellow background or structureless yellow background interspersed with whitish spots.[82,83,84]

Diagnosis of amyloidosis

The demonstration of amyloid in the skin or other organs provides conclusive proof of amyloidosis [Table 2].

Table 2:
Investigations for the diagnosis of amyloidosis.

Investigations performed for the diagnosis include the following:

H & E stain − Sections show small, amorphous globules of eosinophilic material in papillary dermis along with pigmentary incontinence and epidermal changes like hyperkeratosis, acanthosis, hypergranulosis, and parakeratosis.

Special stains − Amyloid stains orange-red with Congo red staining[85] and shows a typical apple-green birefringence under polarized light, a phenomenon called dichroism.[86,87] Other stains which can detect amyloid include PAS, crystal violet, methyl violet, Thioflavin T,[87] and cotton dyes like Pagoda red and Dylon stain.[1,20]

In many instances the amount of amyloid deposit is too scanty to be demonstrated and repeat biopsies are recommended to improve the rate of detection and proper categorization.[78,88]


Antibodies directed against various amyloid fibril proteins help in accurately diagnosing the type of amyloidosis. Macular and lichen amyloidosis are positive for antibodies against cytokeratin K5, and antibodies directed against immunoglobulin light chains are specific for nodular and systemic AL amyloidosis.[89]

Electron microscopy − It provides conclusive proof of the presence of amyloid, wherein typical aggregates of 7 to 10 nm non branching fibrils of amyloid are visualized.[89]

X-ray crystallography and infrared spectroscopy reveal the characteristic cross-β-pleated sheet configuration.[90]

Direct Immunofluorescence − DIF is another valuable adjunctive test to confirm cutaneous amyloidosis. Both macular and lichen amyloidosis show positive immunofluorescence with IgM, C3, and IgA in basement membrane zone and papillary dermis. They may fluoresce in oval, amorphous, or colloid pattern. The results obtained by DIF are comparable to Congo red staining.[91,92,93,94,95]


Cutaneous amyloidosis is a recalcitrant condition, refractory to most of the treatment options available. A wide range of treatment options are employed in the treatment of PLCA. None of these modalities is uniformly effective. Treatment is directed towards the two major problems of pruritus and hyperpigmentation. Since pruritus is believed to induce amyloid deposits, it is important to break the itch-deposition-itch cycle and thus many therapies are directed against pruritus.

Medical management

In mild cases of LA, potent topical steroids alone, or under occlusion or in combination with salicylic acid may help. Intralesional steroids have been tried in localized disease.[96]

Topical DMSO was reported to be effective in MA, LA, and biphasic amyloidosis.[97,98] Intermittent therapy was found to be sufficient as maintenance treatment after reduction of pruritus with daily application of topical DMSO. There was significant reduction of pruritus, pigmentation, and papules.[99] The side-effects of therapy were contact urticaria, desquamation, burning sensation, and garlic-like breath odor. Other authors found treatment with DMSO to be unsatisfactory, with only transient and partial results.[100,101]

Phototherapy is an alternative safe option in the management of PLCA. NbUVB therapy was reported to be very effective in both MA and LA.[102,103] PUVA, topical psoralen with Ultraviolet A was also found to be of benefit, especially with regards to the resolution of pruritus in LA.[104] Topical tacrolimus 0.01% and topical corticosteroids were used to enhance the response of NbUVB.[105,106] Re-PUVA, a combination of acitretin with bath PUVA, was used with success to reduce the pruritus and the papules in LA.[107]

Retinoids − Oral etretinate, 1 mg/kg/day,[108,109,110] acitretin, 0.5 mg/kg/day,[111,112,113,114] were reported to reduce pruritus and flatten the papules in LA. Four to six months treatment is required to see results.[114] Oral isotretinoin[115] and alitretinoin,[116] were successfully used in LA. Tocoretinate, a hybrid compound of retinoic acid and tocopherol, was shown to be beneficial in both LA and MA lesions in a case series involving 10 patients.[117] Topical calcipotriol,[118] topical tacrolimus 0.1%,[119] oral low dose cyclophosphamide,[120] oral cyclosporin,[43,121,122] have been tried with varying degrees of success.

Chemical peels like 15% Trichloracetic acid and 50% Glycolic acid have been found to be beneficial in both MA and LA.

Laser treatments:

CO2 and Nd:YAG lasers are both effectively used in PLCA. Esmat et al.[123] reported a significant reduction in pigmentation, thickness of the lesions, itching, and amyloid deposits in a study population of 25 patients of LA and MA after using fractional ablative CO2 laser. Good improvement with reduction in itching with CO2 laser was demonstrated by Norisugi et al.[124] in two patients of LA on the legs.

Ostovari et al.[125] treated a group of 20 female patients suffering with MA using Q switched Nd:YAG laser and showed an effective reduction of pigmentation in all. They concluded that 532 nm was more efficacious than 1064 nm, Liu et al.[126] showed very good results in a patient of LA by using Q-switched frequency doubled Nd:YAG (532 nm) laser.

Pulsed dye laser has been shown to be beneficial in MA,[127] LA,[128] and NA.[129]

Surgical management

Surgical procedures are generally preferred for NA and sometimes for LA. Various procedures like dermabrasion,[130] scraping with a scalpel,[131] electrodesiccation,[132] have been tried with clearance of LA lesions.

Future directions

Small-fiber neuropathy has been found in patients with lichen amyloidosis, which leads to a reduction in intraepidermal nerve fibers. Increased epidermal expression of IL31 receptors further renders the remaining cutaneous nerve fibers to become hypersensitive and leads to the pruritus in LA.[65,133] IL 31 has been demonstrated to be a mediator of pruritus and therefore, Nemolizumab, a humanized antibody against IL31RA has the potential to become a treatment option for patients with PLCA.[23] Capsaicin may achieve an anti-prurigenic effect by overstimulating and exhausting the cutaneous histamine-sensitive and mechanosensitive C and Aδ fibers.[134] Zeidler et al.[135] demonstrated impressive results in two patients of LA with the help of 8% capsaicin patch. Another possible area of research could be development of therapies aimed at the OSMR β expressing cutaneous nerves.[23]

What is new

The role of dermoscopy and immuno-fluorescence in the diagnosis of cutaneous amyloidosis is becoming more important. The dermoscopic features of nodular amyloidosis have been delineated recently. Recent developments like changes in the epidermal nerve fiber density which is altered in amyloidosis and the role of C fibers in the pathogenesis of PCLA are important contributory factors in the etiology. This recent understanding could lead to novel and more effective targeted approach towards amelioration of this recalcitrant condition. The role of OSMR β expressing cutaneous nerves as another area of interest is highlighted.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1. Breathnach SM. Amyloid and amyloidosis J Am Acad Dermatol. 1988;18(1 pt 1):1–16
2. Freudenthal W. Amyloid in der Haut Arch f Dermat. 1930;162:40–94
3. Wong CK. History and modern concepts Clin Dermatol. 1990;8:1–6
4. Palitz Ll, Peck S. Amyloidosis cutis: a macular variant AMA Arch Dermatol Syphilol. 1952;65:451–7
5. Sakuma TH, Hans-Filho G, Arita K, et al Familial primary localized cutaneous amyloidosis in Brazil Arch Dermatol. 2009;145:695–9
6. Tan T. Epidemiology of primary cutaneous amyloidoses in Southeast Asia Clin Dermatol. 1990;8:20–4
7. Ollague W, Ollague J, Ferretti H. Epidemiology of primary cutaneous amyloidoses in South America Clin Dermatol. 1990;8:25–9
8. Rasi A, Khatami A, Javaheri SM. Macular amyloidosis: an assessment of prevalence, sex, and age Int J Dermatol. 2004;43:898–9
9. Sipe JD, Benson MD, Buxbaum JN, et al Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines Amyloid. 2016;23:209–13
10. Buxbaum JN, Tagoe CE. The genetics of the amyloidoses Annu Rev Med. 2000;51:543–69
11. Wong CK. Cutaneous amyloidoses Int J Dermatol. 1987;26:273–7
12. Somani VK, Hari S, Sita VN, Razvi F. Nylon friction dermatitis: a distinct subset of macular amyloidosis Indian J Dermatol Venereol Leprol. 1995;61:145–7
13. Onuma L, Vega M, Arenas R, Dominguez L. Friction amyloidosis Int J Dermatol. 1994;33:74
14. Siragusa M, Ferri R, Cavallari V, Schepis C. Friction melanosis, friction amyloidosis, macular amyloidosis, towel melanosis: many names for the same clinical entity Eur J Dermatol. 2001;11:545–8
15. Shanon J. Cutaneous amyloidosis associated with atopic disorders Dermatology. 1970;141:297–302
16. Drago F, Ranieri E, Pastorino A, Casazza S, Crovato F, Rebora A. Epstein-Barr virus‐related primary cutaneous amyloidosis. Successful treatment with acyclovir and interferon‐alpha Br J Dermatol. 1996;134:170–4
17. Chang YT, Liu HN, Wong CK, Chow KC, Chen KY. Detection of Epstein‐Barr virus in primary cutaneous amyloidosis Br J Dermatol. 1997;136:823–6
18. Hashimoto K, Ito K, Taniguchi Y, Yang F, Youngberg G. Keratin in cutaneous amyloidoses Clin Dermatol. 1990;8:55–65
19. Touart DM, Sau P. Cutaneous deposition diseases. Part I J Am Acad Dermatol. 1998;39:149–71
20. Black MM. Lipoid proteinosis; metabolic and nutritional disorders Rook/Wilkinson/Ebling: Textbook of Dermatology.. 19986th ed. Oxford, England Blackwell Science:2626–37
21. Arita K, South AP, Hans-Filho G, et al Oncostatin M receptor-β mutations underlie familial primary localized cutaneous amyloidosis Am J Hum Genet. 2008;82:73–80
22. Lin MW, Lee DD, Liu TT, et al Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis Eur J Hum Genet. 2010;18:26–32
23. Lu P, Wu FF, Rong ZL, et al Clinical and genetic features of Chinese patients with lichen and macular primary localized cutaneous amyloidosis Clin Exp Dermatol. 2019;44:e110–7
24. Chang YT, Lin CH, Lee CT, et al Detection of common mutations in sporadic primary localized cutaneous amyloidosis by DNA mass spectrometry Br J Dermatol. 2014;170:974–6
25. Venkataram MN, Bhushnurmath SR, Muirhead DE, Al‐Suwaid AR. Frictional amyloidosis: a study of 10 cases Aust J Dermatol. 2001;42:176–9
26. Hashimoto K, Ito K, Kumakiri M, Headington J. Nylon brush macular amyloidosis Arch Dermatol. 1987;123:633–7
27. Al‐Ratrout JT, Satti MB. Primary localized cutaneous amyloidosis: a clinicopathologic study from Saudi Arabia Int J Dermatol. 1997;36:428–34
28. Eswaramoorthy V, Kaur I, Das A, Kumar B. Macular amyloidosis: etiological factors J Dermatol. 1999;26:305–10
29. Shanon J, Sagher F. Interscapular cutaneous amyloidosis Arch Dermatol. 1970;102:195–8
30. Kibbi Ag, Rubeiz Ng, Zaynoun St, Kurban AK. Primary localized cutaneous amyloidosis Int J Dermatol. 1992;31:95–8
31. Hartshorne S. Familial primary cutaneous amyloidosis in a South African family Clin Exp Dermatol. 1999;24:438–42
32. Verga U, Fugazzola L, Cambiaghi S, et al Frequent association between MEN 2A and cutaneous lichen amyloidosis Clin Endocrinol. 2003;59:156–61
33. Ogiyama Y, Hayashi Y, Kou C, Matsumoto Y, Ohashi M. Cutaneous amyloidosis in patients with progressive systemic sclerosis Cutis. 1996;57:28–32
34. Chanoki M, Suzuki S, Hayashi Y, Ishii M, Hamada T. Progressive systemic sclerosis associated with cutaneous amyloidosis Int J Dermatol. 1994;33:648–9
35. Black MM. The ultrastructure of primary localized cutaneous amyloidosis in systemic sclerosis Trans St Johns Hosp Dermatol Soc. 1972;58:178
36. Black MM. Primary localised cutaneous amyloidosis in systemic sclerosis Trans St Johns Hosp Dermatol Soc. 1971;57:177
37. Azoan‐Masoliver A. Widespread primary localized eutaneous amyloidosis (maeutar form) associated with systemic sclerosis Br J Dermatol. 1995;132:163–5
38. Danielsen L, Christensen HE, Wanstrup J. Cutaneous amyloidosis: classification, pathogenesis and relation to “Collagen Disease” Acta Pathol Microbiol Scand Sect A Pathol. 1970;78:335–44
39. Jhingan A, Lee JS, Kumarasinghe SP. Lichen amyloidosis in an unusual location Singapore Med J. 2007;48:e165–7
40. Tafarel JR, Lemos LB, Oliveira PM, Lanzoni VP, Ferraz ML. Cutaneous amyloidosis associated with primary biliary cirrhosis Eur J Gastroenterol Hepatol. 2007;19:603–5
41. Fujiwara K, Kono T, Ishii M, et al Primary localized cutaneous amyloidosis associated with autoimmune cholangitis Int J Dermatol. 2000;39:768–71
42. Danno K, Horio T, Miyachi Y, Hayakawa M, Takatsuki K. Coexistence of Kimura’s disease and lichen amyloidosus in three patients Arch Dermatol. 1982;118:976–80
43. Teraki Y, Katsuta M, Shiohara T. Lichen amyloidosus associated with Kimura’s disease: successful treatment with cyclosporine Dermatology. 2002;204:133–5
44. Apaydin R, Bilen N, Bayramgürler D, Harova G, Çetinarslan B. Lichen amyloidosis, ankylosing spondylitis and autoimmune thyroiditis: coincidence or association? J Eur Acad Dermatol Venereol. 2000;14:135–7
45. Dahdah MJ, Kurban M, Kibbi AG, Ghosn S. Primary localized cutaneous amyloidosis: a sign of immune dysregulation? Int J Dermatol. 2009;48:419–21
46. Nakjang YS, Sivavathorn A, Reungsinpinya S, Yutthanawiwat T. Biphasic amyloidosis: a clinicopathological and histochemical study Aust J Dermatol. 1982;23:82–6
47. Tanigaki T, Hata S, Kitano Y, et al Unusual pigmentation on the skin over trunk bones and extremities Dermatology. 1985;170:235–9
48. Kandhari R, Ramesh V, Singh A. Asymptomatic conchal papules Indian J Dermatol Venereol Leprol. 2013;79:445
49. Liu C, Ding LJ, Tan C. Brownish macules on the right temple J Cosmet Dermatol. 2020;19:1479–80
50. Bandhlish A, Aggarwal A, Koranne RV. A clinico-epidemiological study of macular amyloidosis from north India Indian J Dermatol. 2012;57:269
51. Chuang YY, Lee DD, Lin CS, et al Characteristic dermoscopic features of primary cutaneous amyloidosis: a study of 35 cases Br J Dermatol. 2012;167:548–54
52. Ho MH, Chong LY. Poikiloderma‐like cutaneous amyloidosis in an ethnic Chinese girl J Dermatol. 1998;25:730–4
53. Unni M, Ankad B, Naidu V, Rao KS. A familial poikiloderma-like cutaneous amyloidosis Indian J Dermatol. 2014;59:633
54. Chandran NS, Goh BK, Lee SS, Goh CL. Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma‐like, dyschromic and bullous variants J Dermatol. 2011;38:1066–71
55. Bourke JF, Berth‐Jones J, Burns DA. Diffuse primary cutaneous amyloidosis Br J Dermatol. 1992;127:641–4
56. Suranagi VV, Siddramappa BS, Bannur HB, Patil PV, Davangeri RS. Bullous variant of familial biphasic lichen amyloidosis: a unique combination of three rare presentations Indian J Dermatol. 2015;60:105
57. Black Mm, Maibach HI. Macular amyloidosis simulating naevoid hyperpigmentation Br J Dermatol. 1974;90:461–4
58. Abbas O, Ugent S, Borirak K, Bhawan J. Linear macular amyloidosis J Eur Acad Dermatol Venereol. 2009;23:1446–8
59. Madarasingha NP, Satgurunathan K, De Silva MV. A rare type of primary cutaneous amyloidosis: amyloidosis cutis dyschromica Int J Dermatol. 2010;49:1416–8
60. Wu JJ, Su YN, Hsiao CH, Jee SH, Tjiu JW, Chen JS. Macular amyloidosis presenting in an incontinentiapigmenti-like pattern with subepidermal blister formation J Eur Acad Dermatol Venereol. 2008;22:635–7
61. Wang WJ. Clinical features of cutaneous amyloidoses Clin Dermatol. 1990;8:13–9
62. Black MM. Lichen amyloidosus. An unusual clinical variant associated with the Koebner phenomenon Acta Derm Venereol. 1972;52:51–4
63. Sagi L, Trau H. The koebner phenomenon Clin Dermatol. 2011;29:231–6
64. Cai D, Li Y, Zhou C, Jiang Y, Jiao J, Wu L. Comparative proteomics analysis of primary cutaneous amyloidosis Exp Ther Med. 2017;14:3004–12
65. Tey HL, Cao T, Nattkemper LA, Tan VW, Pramono ZA, Yosipovitch G. Pathophysiology of pruritus in primary localized cutaneous amyloidosis Br J Dermatol. 2016;174:1345–50
66. Kurban Ak, Malak Ja, Afifi Ak, Mire J. Primary localized macular, cutaneous amyloidosis: histochemisthy and electron microscopy Br J Dermatol. 1971;85:52–60
67. Brownstein MH, Hashimoto K. Macular amyloidosis Arch Dermatol. 1972;106:50–7
68. Black MM. Primary localized amyloidosis of the skin: clinical variants, histochemistry and ultrastructure Amyloidosis. 1976:479–513
69. Hicks BC, Weber PJ, Hashimoto K, Ito K, Koreman DM. Primary cutaneous amyloidosis of the auricular concha J Am Acad Dermatol. 1988;18:19–25
70. Mun KS, Pailoor J, Reddy SC. Primary localised deep cutaneous amyloidosis of the eyelid Malays J Pathol. 2005;27:113–5
71. Northcutt AD, Vanover MJ. Nodular cutaneous amyloidosis involving the vulva: case report and literature review Arch Dermatol. 1985;121:518–21
72. Inazumi T, Hakuno M, Yamada H, et al Characterization of the amyloid fibril from primary localized cutaneous nodular amyloidosis associated with Sjögren’s syndrome Dermatology. 1994;189:125–8
73. Srivastava M. Primary cutaneous nodular amyloidosis in a patient with Sjögren’s syndrome J Drugs Dermatol. 2006;5:279–80
74. Yoneyama K, Tochigi N, Oikawa A, Shinkai H, Utani A. Primary localized cutaneous nodular amyloidosis in a patient with Sjögren’s syndrome: a review of the literature J Dermatol. 2005;32:120–3
75. Konishi A, Fukuoka M, Nishimura Y. Primary localized cutaneous amyloidosis with unusual clinical features in a patient with Sjögren’s syndrome J Dermatol. 2007;34:394–6
76. Meijer JM, Schonland SO, Palladini G, et al Sjögren’s syndrome and localized nodular cutaneous amyloidosis: coincidence or a distinct clinical entity? Arthritis Rheuma. 2008;58:1992–9
77. Summers EM, Kendrick CG. Primary localized cutaneous nodular amyloidosis and CREST syndrome: a case report and review of the literature Cutis. 2008;82:55
78. Caruana D, McCusker S, Harper C, Bilsland D. Curious facial plaque diagnosed as nodular primary localised cutaneous amyloidosis BMJ Case Rep. 2019;12:e228163
79. Kalajian AH, Waldman M, Knable AL. Nodular primary localized cutaneous amyloidosis after trauma: a case report and discussion of the rate of progression to systemic amyloidosis J Am Acad Dermatol. 2007;57:S26–9
80. Lee DY, Kim YJ, Lee JY, Kim MK, Yoon TY. Primary localized cutaneous nodular amyloidosis following local trauma Ann Dermatol. 2011;23:515–8
81. Woollons A, Black MM. Nodular localized primary cutaneous amyloidosis: a long‐term follow‐up study Br J Dermatol. 2001;145:105–9
82. Rongioletti F, Atzori L, Ferreli C, Pinna A, Aste N, Pau M. A unique dermoscopy pattern of primary cutaneous nodular amyloidosis mimicking a granulomatous disease J Am Acad Dermatol. 2016;74:e9–10
83. Meo ND, Noal C, Fadel M, Trevisan G. Yellow teardrop-like structures in primary nodular skin amyloidosis G Ital Dermatol Venereol. 2018;153:118–9
84. Atzori L, Ferreli C, Matucci-Cerinic C, Pilloni L, Rongioletti F. Primary localized cutaneous nodular amyloidosis and limited cutaneous systemic sclerosis: additional cases with dermatoscopic and histopathological correlation of amyloid deposition Dermatopathology. 2021;8:229–35
85. Puchtler HO, Sweat FA. Congo red as a stain for fluorescence microscopy of amyloid J Histochem Cytochem. 1965;13:693–4
86. Glenner GG. The bases of the staining of amyloid fibers: their physico-chemical nature and the mechanism of their dye-substrate interaction Prog Histochem Cytochem. 1981;13:1–37
87. Hobbs JR, Morgan AD. Fluorescence microscopy with thioflavine‐T in the diagnosis of amyloid J Pathol Bacteriol. 1963;86:437–42
88. Jowkar F, Kahnooj MH, Aslani FS, Parvizi MM. Clinicopathological evaluation of patients with rippled pattern pigmentation of the skin: a single‐center study Dermatol Ther. 2020;33:e13278
89. Schreml S. Cutaneous amyloidoses Rook’s Textbook of Dermatology. 2016:1–6
90. Glenner GG. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts) N Engl J Med. 1980;302:1283–92
91. MacDonald DM, Black MM, Ramnarain N. Immunofluorescence studies in primary localized cutaneous amyloidosis Br J Dermatol. 1977;96:635–41
92. Salim T, Shenoi SD, Balachandran C, Mehta VR. Lichen amyloidosus: a study of clinical, histopathologic and immunofluorescence findings in 30 cases Indian J Dermatol Venereol Leprol. 2005;71:166
93. Habermann MC, Montenegro MR. Primary cutaneous amyloidosis: clinical, laboratorial and histopathological study of 25 cases Dermatology. 1980;160:240–8
94. Mehrotra K, Dewan R, Kumar JV, Dewan A. Primary cutaneous amyloidosis: a clinical, histopathological and immunofluorescence study J Clin Diagnos Res. 2017;11:WC01
95. Yadav A, Garg T, Mandal AK, Chander R, Yadav A. Immunofluorescence and immunohistochemistry in macular amyloidosis: an observational study Indian Dermatol Online J. 2017;8:499
96. Breathnach SM. The cutaneous amyloidoses: pathogenesis and therapy Arch Dermatol. 1985;121:470–5
97. Monfrecola G, Iandoli R, Bruno G, Martellotta D. Lichen amyloidosus: a new therapeutic approach Acta Derm Venereol. 1985;65:453
98. Pravata G, Pinto G, Bosco M, Noto G, Arico M. Unusual localization of lichen amyloidosus. Topical treatment with dimethylsulfoxide Acta Derm Venereol. 1989;69:259
99. Özkaya‐Bayazit E, e Kavak A, Güngör H, Özarmagan G. Intermittent use of topical dimethyl sulfoxide in macular and papular amyloidosis Int J Dermatol. 1998;37:949–54
100. Kobayashi T, Yamasaki Y, Watanabe T, Onoda N. Extensive lichen amyloidosus refractory to DMSO J Dermatol. 1995;22:755–8
101. Pandhi R, Kaur I, Kumar B. Lack of effect of dimethylsulphoxide in cutaneous amyloidosis J Dermatol Treat. 2002;13:11–4
102. Alonso-González J, Rodríguez-Granados MT, Toribio J. Satisfactory response to narrowband UV-B therapy in generalized lichen amyloidosis Actas Dermo-Sifiliográf. 2013;6:527–9
103. Hudson LD. Macular amyloidosis: treatment with ultraviolet B Cutis.. 1986;38:61
104. Goon Teik Jin A, Por A, Khoo Shih Wee L, Kwok Yew Kai C, Leok GC. Comparative study of phototherapy (UVB) vs. photochemotherapy (PUVA) vs. topical steroids in the treatment of primary cutaneous lichen amyloidosis Photodermatol Photoimmunol Photomed. 2001;17:42–3
105. Oiso N, Yudate T, Kawara S, Kawada A. Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy, topical corticosteroids and an antihistamine Clin Exp Dermatol. 2009;34:e833–6
106. Kalkan G, Markoc F, Bas Y. An alternative treatment model: the combination therapy of narrow band ultraviolet B phototherapy and tacrolimus ointment 0.1% in biphasic amyloidosis J Pak Med Assoc. 2014;64:579–82
107. Grimmer J, Weiss T, Weber L, Meixner D, Scharffetter‐Kochanek K. Successful treatment of lichen amyloidosis with combined bath PUVA photochemotherapy and oral acitretin Clin Exp Dermatol. 2007;32:39–42
108. David M, Ingber A, Ben-Chetrit A, Sandbank J, Sandbank M. Effect of etretinate on lichen amyloidosus Dermatology. 1987;175:302–3
109. Helander I, Hopsu‐Havu VK. Treatment of lichen amyloidosus by etretinate Clin Exp Dermatol. 1986;11:574–7
110. Marschalkó M, Daróczy J. Etretinate for the treatment of lichen amyloidosis Arch Dermatol. 1988;124:657–9
111. Carlesimo M, Narcisi A, Orsini D, et al A case of lichen amyloidosus treated with acitretin Clin Ter. 2011;162:e59–61
112. Choi JY, Sippe J, Lee S. Acitretin for lichen amyloidosus Australas J Dermatol. 2008;49:109–13
113. Reider N, Sepp N, Fritsch P. Remission of lichen amyloidosus after treatment with acitretin Dermatology. 1997;194:309–11
114. Hernandez‐Nunez A, Dauden E, Moreno de Vega MJ, Fraga J, Aragüés M, García‐Díez A. Widespread biphasic amyloidosis: response to acitretin Clin Exp Dermatol. 2001;26:256–9
115. Atacan D, Ergin C, Çelik G, Gönül M, Adabağ A. Oral isotretinoin: a new treatment alternative for generalized lichen amyloidosis Australas J Dermatol. 2016;57:246
116. Tietze JK, Heppt MV, Flaig MJ, Thomas P. Successful treatment of lichen amyloidosus with oral alitretinoin J Eur Acad Dermatol Venereol. 2016:884–5
117. Terao M, Nishida K, Murota H, Katayama I. Clinical effect of tocoretinate on lichen and macular amyloidosis J Dermatol. 2011;38:179–84
118. Khoo BP, Tay YK, Goh CL, Centre FT. Calcipotriol ointment vs. betamethasone 17‐valerate ointment in the treatment of lichen amyloidosis Int J Dermatol. 1999;38:539–41
119. Castanedo-Cazares JP, Lepe V, Moncada B. Lichen amyloidosis improved by 0.1% topical tacrolimus Dermatology. 2002;205:420–1
120. Das J, Gogoi RK. Treatment of primary localised cutaneous amyloidosis with cyclophosphamide Indian J Dermatol Venereol Leprol. 2003;69:163
121. Behr FD, Levine N, Bangert J. Lichen amyloidosis associated with atopic dermatitis: clinical resolution with cyclosporine Arch Dermatol. 2001;137:553–5
122. Cho TH, Lee MH. A case of lichen amyloidosus accompanied by vesicles and dyschromia Clin Exp Dermatol. 2008;33:291–3
123. Esmat SM, Fawzi MM, Gawdat HI, Ali HS, Sayed SS. Efficacy of different modes of fractional CO2 laser in the treatment of primary cutaneous amyloidosis: a randomized clinical trial Lasers Surg Med. 2015;47:388–95
124. Norisugi O, Yamakoshi T, Shimizu T. Successful treatment of lichen amyloidosis using a CO2 surgical laser Dermatol Ther. 2014;27:71–3
125. Ostovari N, Mohtasham N, Oadras MS, Malekzad F. 532‐nm and 1064 ‐nm Q‐switched Nd: YAG laser therapy for reduction of pigmentation in macular amyloidosis patches J Eur Acad Dermatol Venereol. 2008;22:442–6
126. Liu HT. Treatment of lichen amyloidosis (LA) and disseminated superficial porokeratosis (DSP) with frequency‐doubled Q‐switched Nd: YAG laser Dermatol Surg. 2000;26:958–62
127. Barsky M, Buka RL. Pulsed dye laser for the treatment of macular amyloidosis: a case report Cutis. 2014;93:189
128. Sawamura D, Sato‐Matsumura KC, Shibaki A, Akiyama M, Kikuchi T, Shimizu H. A case of lichen amyloidosis treated with pulsed dye laser J Eur Acad Dermatol Venereol. 2005;19:262–3
129. Alster TS, Manaloto RM. Nodular amyloidosis treated with a pulsed dye laser Dermatol Surg. 1999;25:133–5
130. Savant SS. Therapeutic regional dermabrasion in papular lichen amyloidosis of shins Indian J Dermatol Venereol Leprol. 1995;61:196–201
131. Harahap M, Perkasa Marwali MR. The treatment of lichen amyloidosis: a review and a new technique Dermatol Surg. 1998;24:251–4
132. Aoki M, Kawana S. Lichen amyloidosis of the auricular concha: successful treatment with electrodesiccation J Dermatol. 2009;36:116–7
133. Maddison B, Namazi MR, Samuel LS, et al Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus Br J Dermatol. 2008;159:403–6
134. Bautista DM, Wilson SR, Hoon MA. Why we scratch an itch: the molecules, cells and circuits of itch Nat Neurosci. 2014;17:175
135. Zeidler C, Metze D, Ständer S. Successful treatment of lichen amyloidosis using capsaicin 8% patch J Eur Acad Dermatol Venereol. 2016;7:1236–8

amyloid; amyloidosis; cutaneous; pruritus; pigmentation

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