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Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 17-23

A clinicopathologic study of cutaneous amyloidosis at a tertiary health care center in South India

1 Department of Dermatology, Sri Ramachandra University, Chennai, Tamil Nadu, India
2 Department of Pathology, Sri Ramachandra University, Chennai, Tamil Nadu, India

Date of Web Publication17-Jun-2016

Correspondence Address:
Dr. Aditya Kumar Bubna
Department of Dermatology, Sri Ramachandra University, Porur, Chennai - 600 116, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2349-5847.184255

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Background: Primary cutaneous amyloidosis (PCA) is quite a common disorder seen in Southeast Asia. It is characterized by amorphous eosinophilic deposits of a fibrillar protein in the dermis without any systemic involvement. However, the etiology for this disease still remains elusive without much satisfying outcomes with the currently available treatments. Aim: To study the clinical and demographic patterns of PCA and correlate it with histopathological findings along with polarized microscopy examination. Methods: A cross-sectional study done over a 1½ years period wherein after patient enrollment, they underwent a thorough clinical evaluation followed by a skin biopsy and complemented by polarized microscopy. Results: A prevalence of 0.04% and a female preponderance (61.76%) was observed. Lichen amyloidosis (LA) was more common than macular amyloidosis (MA). Majority of patients presented between 41 and 50 years. There was a significant association of pruritus and friction with PCA. The most common sites involved were shins for LA and interscapular area for MA. On histology, epidermal changes were not so significant for MA. However, hyperkeratosis and acanthosis were major epidermal findings for LA. Lymphohistiocytic infiltrates were common dermal changes for both variants of amyloidosis. Amyloid deposits appeared as eosinophilic fissured masses under light microscopy on hematoxylin and eosin staining. Conclusion: PCA is a disorder of middle age seen more commonly in females. Pruritus and friction demonstrate significant contribution in the development of PCA. Whether there is an association of PCA with diabetes mellitus, hypertension, bronchial asthma, and hypothyroidism needs further consideration.

Keywords: Congo red, friction, lichen amyloidosis, macular amyloidosis, polarized microscopy

How to cite this article:
Jayabhanu AA, Bubna AK, Rangarajan S, Veeraraghavan M, Joseph LD, Sundaram M. A clinicopathologic study of cutaneous amyloidosis at a tertiary health care center in South India. Pigment Int 2016;3:17-23

How to cite this URL:
Jayabhanu AA, Bubna AK, Rangarajan S, Veeraraghavan M, Joseph LD, Sundaram M. A clinicopathologic study of cutaneous amyloidosis at a tertiary health care center in South India. Pigment Int [serial online] 2016 [cited 2023 Mar 30];3:17-23. Available from: https://www.pigmentinternational.com/text.asp?2016/3/1/17/184255

  Introduction Top

Amyloid is an abnormal fibrillar proteinaceous material that gets deposited in tissues.[1] When there is amyloid deposition in apparently normal skin without affecting any internal organ, the term primary cutaneous amyloidosis (PCA) has been employed. Phenotypically, there have been many presentations of PCA. The three major types of PCA include lichen amyloidosis (LA) [Figure 1] and [Figure 2], macular amyloidosis (MA) [Figure 3], and nodular amyloidosis. When LA and MA coexist, then it is referred to as biphasic amyloidosis (BA).[2] Other variants of PCA include bullous, poikilodermic,[3] vitiliginous, and anosacral types. The etiopathogenesis of PCA still remains elusive though there have been many suggestions for the same. These include various risk factors such as female gender,[4],[5] racial factors,[6] exposure to solar radiation,[7] friction,[8],[9] atopy,[10] and autoimmunity.[11] A high incidence of the lichen and macular variants of PCA have been reported in Southeast Asia and Latin America.[12],[13] Rarely, association of PCA with autoimmune connective tissue disorders and primary biliary cirrhosis has been described.[1] Histologic sections of PCA stained with hematoxylin and eosin, reveal aggregates of homogenous and eosinophilic dermal deposits. On staining with Congo red, and examining the specimen under polarized microscopy an apple green birefringence is observed, a specific finding to confirm the diagnosis of amyloidosis. Our study was carried out to determine the prevalence of PCA among the dermatology patients at our center, along with a clinicopathologic correlation of PCA, utilizing polarized microscopy, and Congo red staining to further substantiate our findings.
Figure 1: Pigmented papules as seen in lichen amyloidosis

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Figure 2: A closer view demonstrating the papules of lichen amyloidosis with a keratotic texture

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Figure 3: Rippled pattern of hyperpigmentation as observed in macular amyloidosis

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  Methods Top

This was a cross-sectional hospital-based study done in the Department of Dermatology, in our institute from January 2013 to June 2014, conducted to assess the prevalence of PCA among all patients attending our outpatient department and to evaluate the common morphological patterns and sites of involvement along with any associated symptoms and relationship to an underlying systemic affection. The study population included all the 68 clinically diagnosed cases of PCA that attended the dermatology outpatient department during the study period. After enrolling the population in our study, a detailed history and clinical examination was done for all patients with regard to the clinical type of PCA, etiological factors involved, duration of disease, presenting symptoms, and associated systemic disease. Following an informed consent, all 68 patients were subjected to a skin biopsy which was first stained with hematoxylin and eosin and visualized under light microscopy. This was succeeded by Congo red staining and examination under polarized microscope. As all variables in our study were qualitative, they were expressed as percentage values.

  Results Top

During our study from January 2013 to June 2014, out of the 170,579 patients who attended our dermatology outpatient department, 68 were diagnosed to have PCA with a prevalence of 0.04% during the study period. Out of the 68 patients, 42 were females and 26 males. In our study, only two clinical types of PCA were identified. About 38 patients were identified with LA and the remaining 30 had MA. Majority of the patients belonged to the age group of 41–50 years, followed by 31–40 years with succeeding equal numbers of patients in the 21–30 years and 51–60 years. About 40 patients in our study had the disease for 1–5 years, followed by 14 patients who had the disease for 6 months to a year thereby signifying the chronicity of PCA. Out of the 30 patients of MA, 21 patients had associated pruritus, along with rippled hyperpigmentation of the skin, whereas the remaining nine had only cutaneous pigmentation. In all 38 patients of LA, pruritus was a significant feature detected, along with skin pigmentation. Out of the 68 patients, only 2 had an associated familial association. Risk of a frictional component was identified in 54 of the 68 patients in our study. The major abrasive tool utilized were vegetable fiber in 28 patients, plastic comb in 15 patients, sacred thread in 6 patients, nylon brush in 3 patients, and pumice stone in 2 patients. The most common location for LA was pretibial, followed equally by the extensor aspect of the forearm and upper arm. In MA, the most common site was the interscapular area, followed by the extensor aspect of forearms and upper arms, pretibial region, and thigh. Associated diabetes mellitus (DM) was seen in 39 patients, out of which 38 had LA and 1 MA. Hypertension was seen in 20 patients having LA and 5 with MA. Bronchial asthma was an associated finding in 10 patients, all with LA and hypothyroidism in 1 patient again with LA. The entire demographic data of our patients have been lucidly summarized in [Table 1].
Table 1: Clinico-demographic data of our patients

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With respect to our histopathology data, out of the 30 clinically diagnosed cases of MA, deposits of dermal amyloid were identified in 20 (66.67%) patients, whereas out of the 38 clinical cases of LA, 22 (57.89%) patients demonstrated amyloid by both hematoxylin and eosin [Figure 4] and [Figure 5] as well as Congo red staining [Figure 6] and [Figure 7] and polarized microscopy examination [Figure 8]. The major epidermal features seen in the 20 histologically positive cases of MA were normal epidermis (60%), followed by acanthosis (40%), elongated rete ridges (25%), increased basal cell layer pigmentation (25%), papillomatosis (20%), hypermelanosis (15%), hyperkeratosis (15%), and degeneration of basal cell layer (10%). In the dermis, the changes witnessed included lymphohistiocytic infiltrates (90%), pigment incontinence (30%), and increased collagen deposition (10%). Out of the 38 clinically diagnosed cases of LA, amyloid deposits were identified in 22 (57.89%) patients. The major epidermal change observed was hyperkeratosis (90.90%), followed by acanthosis (72.71%), degeneration of basal cell layer (18.2%), elongated rete ridges (13.63%), parakeratosis (9.09%), and papillomatosis (4.54%). The dermal changes were lymphohistiocytic infiltrates (50%), pigment incontinence (22.72%), and increased dermal collagen (18.2%).
Figure 4: Eosinophilic amorphous aggregates of amyloid seen on hematoxylin and eosin staining (H and E, ×100)

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Figure 5: Epidermal hyperkeratosis and acanthosis along with dermal amyloid deposits seen in lichen amyloidosis (H and E, ×100)

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Figure 6: Epidermal hyperkeratosis, acanthosis, and mild papillomatosis with dermal deposits of amyloid on Congo red staining under light microscopy (×100)

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Figure 7: Congo red stain showing deposits of amyloid in the dermis under light microscopy (×200)

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Figure 8: Amyloid deposits demonstrating apple green birefringence on polarized microscopy following Congo red staining

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  Discussion Top

Our study was an attempt to evaluate the major types of PCA present in our setting, to study the various demographic patterns associated with it and carefully observe the histopathologic characteristics of PCA. We also wanted to compare our findings with major studies of PCA done in India and abroad with more emphasis on studies done in India.

During our 1½ year study period, we clinically diagnosed 68 patients with PCA, out of which 42 (61.76%) were confirmed on histologic examination. Similar studies done from India by Krishna et al.,[14] and Vijaya et al.[15] demonstrated an amyloid-positive histology in 61.29% and 71.11% of their clinically diagnosed cases of PCA, which was very similar to our study, thereby indicating no significant difference in its prevalence. However, two studies done abroad from Jakarta [16] and Britain [17] yielded only 78 cases in a 5 year period and 21 cases over 12 years, respectively, thereby portraying a higher prevalence of PCA in our setting.

In our study, 61.76% of the patients were females and the remaining 38.23% were males. Out of the other studies done in India, Krishna et al.,[14] and Bandhlish et al.,[18] like our study demonstrated an increased female preponderance. A heightened female preponderance was also observed in studies from Jordan, Malaysia, South America and Indonesia.[13],[16],[19],[20] However, two studies from the state of Karnataka [15],[21] reported an increased male preponderance. A similar finding was also documented in a study from Taiwan.[22]

Out of the various clinical types of PCA, LA constituted 55.88% of our case load, with MA being 44.11%. Other variants of PCA were not observed in our study. Similarly, Vijaya et al.,[15] Wang et al.,[22] and Looi [20] also demonstrated LA to be the most common form of PCA in their study. However, Krishna et al.[14] disagreed with our findings with MA predominating in their study population. Backing the findings of Krishna et al.[14] were reports from studies conducted by Ozkaya-Bayazit et al.,[23] Black and Jones,[17] Djuanda et al.,[16] and Eswaramoorthy et al.[4] Salient features of this observation are summarized in [Table 2].
Table 2: The occurrence of various types of Primary cutaneous amyloidosis in some of the previous studies in comparison to ours

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The most common age group where PCA occurred in our study population was 41–50 years followed by 31–40 years. This was at par with the Indian study conducted at Agra.[14] A Malaysian and Indonesian study also reiterated the above finding.[16],[20] Other studies done from India did not comment regarding the most common age of the occurrence of PCA.

Duration of the disease seen in our patients ranged from 6 months to more than 5 years. This correlated with other studies done by Salim et al.,[21] Tay and Dacosta,[24] and al-Ratrout and Satti.[5] Salient features for the same have been summarized in [Table 3].
Table 3: The duration of the disease, occurrence of pruritus, familial association and the role of friction in precipitating primary cutaneous amyloidosis in the participants of our study and comparing these features with other studies

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Pruritus was a significant finding in our study, seen in 86.7% of our patients. Similarly, pruritus as an important complaint was also demonstrated by Salim et al.,[21] Bandhlish et al.,[18] Tay and Dacosta,[24] and al-Ratrout and Satti.[5] These findings have been summarized in [Table 3].

Familial association of PCA was only seen in 2.94% of our patients. This was significantly low when compared to the other studies done in India [14],[18],[21] and has been summarized in [Table 3].

Similarly, a genetic association has been described by Eswaramoorthy et al.,[4] and Gagel et al.[25] Rajagopalan and Tay [26] have described 19 cases of LA in a Malaysian Chinese family in 4 generations. However, Looi [20] refuted this association.

Friction as a contributing factor was observed in 79.41% of our patients. Similarly, the role of friction in the pathogenesis of PCA was observed by Salim et al.,[21] Krishna et al.,[14] Bandhlish et al.,[18] and Somani et al.[7] and has been summarized in [Table 3]. This association with friction was much higher with our patients when compared to the previous studies. The role of chronic friction with respect to PCA cannot be completely ignored. This aspect has been further elaborated by Wong and Lin,[27] and Sumitra and Yesudian.[28]

The distribution of lesions in our cases of MA was predominantly seen in the interscapular region (63.33%). In the study from Agra and Delhi, this distribution was 52.63% and 80%, respectively. The predominant sites of involvement in our patients of LA have been summarized in [Table 4] along with the findings of other studies in this regard.[5],[21],[22],[24],[29],[30]
Table 4: Comparison of the distribution patterns of lichen amyloidosis in our study with respect to previous studies

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An association with DM was seen in 57.35% of our patients, hypertension in 36.76%, bronchial asthma in 14.70%, and hypothyroidism in 1.47%. In the study by Salim et al.,[21] an association with DM was seen in 16.7% of patients. Similarly, a Jordanian study an association of 0.83% with DM was noted.[19] Whether there actually is an association with DM, only further studies could help in elucidating this better.

Out of the 68 patients who were clinically diagnosed to have PCA, 42 demonstrated eosinophilic homogeneous aggregates in the dermis which on staining with Congo red and examination under polarized microscopy demonstrated apple green birefringence. Out of these, 20 were MA and 22 were LA cases. In MA, a normal epidermis was the hallmark finding in 60% of patients, followed by acanthosis (40%), rete ridges elongation (25%), basal cell layer pigmentation (25%), hyperkeratosis (15%), hypergranulosis (15%), and degeneration of basal cell layer (10%). Even Bandhlish et al.[18] demonstrated that a normal epidermis was a consistent finding in most of the sections examined in their study. Other features described by them included hyperkeratosis (11.5%) and mild to moderate thinning of the epidermis (27%), a finding contrary to ours wherein acanthosis constituted an important finding. Further Vijaya et al.[15] also demonstrated a normal epidermis in all their cases of MA. In the dermis, a lymphohistiocytic infiltrate was seen in 90% of our cases of MA, followed by pigment incontinence (30%) and increased dermal collagen (20%). An increased lymphohistiocytic infiltrate was also reported by Bandhlish et al.,[18] in 88% of their cases almost similar to our finding. Other findings included melanophages in the upper dermal substance in 15% of the biopsy specimens. No comment apart from dermal amyloid deposits in biopsy specimens were given from the study done by Vijaya et al.[15]

Hallmark features for LA in the epidermis included hyperkeratosis (90.90%) and acanthosis (72.72%). In the dermis, a dense lymphocytic infiltrate constituted the major finding (50%), followed by pigment incontinence (22.72%) and increased dermal collagen (18.18%). Vijaya et al.[15] also demonstrated hyperkeratosis and acanthosis to be their salient findings in the specimens of LA examined. The presence of a lymphohistiocytic infiltrates were only a minor finding here thus differing from our study. Salim et al.[21] demonstrated hyperkeratosis in all their biopsy specimens with acanthosis amounting to 90%, papillomatosis 33.3%, hypergranulosis 16.7%, and elongated rete ridges in 13.3%, therefore differing considerably with our epidermal findings. The dermis was characterized by a dense lymphocytic infiltrate which was seen in 70% of their cases, being 20% < our values.

  Conclusion Top

We conclude that PCA is mainly a disorder of the middle-aged population having a female preponderance. Whether there exists an association with regard to female sex hormones in the etiology of PCA still requires elaboration. LA is the most common variant of PCA, followed by MA with the most common affected sites being pretibial and interscapular regions, respectively. There definitely appears to be some link between DM and PCA. However, the relationship needs proper elucidation. Pruritus and friction appear to have major contribution in the development of PCA. Microscopy in MA is usually associated with a normal epidermis. The major pathology being identified in the dermis with amyloid deposits, lymphohistiocytic infiltrates, and pigmentary incontinence. On the other hand, in LA, epidermal changes warrant mention with hyperkeratosis and acanthosis being characteristic findings. Dermal changes however in LA are almost similar with MA. Finally, though PCA is an easily diagnosable condition, a concrete therapy of the same is still lacking. One reason for this may be associated with the lack of an identifiable specific etiologic factor.

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  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]

  [Table 1], [Table 2], [Table 3], [Table 4]

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