|Year : 2022 | Volume
| Issue : 2 | Page : 133-139
A clinicopathological study of primary cutaneous amyloidosis in tertiary care center, Hubballi
Sanjay Ramachandra Thejaswi1, Mohan Eshwar Rao Shendre2, Chandramohan Kudligi2, Raghavendra Tophakhane3
1 Department of Dermatology, Venereology and Leprosy, The Oxford Medical College Hospital and Research Centre, Bengaluru, Karnataka, India
2 Department of Dermatology, Venereology and Leprosy, Karnataka Institute of Medical Sciences, Hubballi, Karnataka, India
3 Department of Dermatology, Venereology and Leprosy, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
|Date of Submission||05-Nov-2021|
|Date of Decision||21-Dec-2021|
|Date of Acceptance||31-Dec-2021|
|Date of Web Publication||26-Aug-2022|
Mohan Eshwar Rao Shendre
Department of Dermatology, Venereology and Leprosy, Karnataka Institute of Medical Sciences, Hubballi, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Cutaneous amyloidosis has a varied clinical presentations. Clinically, it is difficult to distinguish different subtypes of PCA. Objectives: This study was been taken up to correlate clinicohistological profile of all three forms of primary cutaneous amyloidosis (PCA) and to study various factors affecting the disease. Materials and Methods: A total number of 85 patients of PCA attending Skin and STD in tertiary care center in Hubballi were included in the study. A detailed history was taken, complete general physical, systemic, and cutaneous examination was done, and details of skin lesions were noted. Patient was subjected to skin biopsy from the affected area. Clinicohistological findings so obtained were analyzed, and results were correlated. Results: Out of 85 cases, 36 (42.35%) were macular amyloidosis (MA), 43 (50.58%) lichen amyloidosis (LA), and 6 (7.05%) were biphasic amyloidosis (BA). Majority of the patients were in the age group of 21–50, with a male: female ratio of 1:1.3. History of scrubbing while taking bath was given by 90.58%. Housewives were the most frequently involved group (38.82%). In MA, most frequently involved sites were upper back (58.33%) and extensor aspect of arm (55.55%). In LA, majority had involvement of the pretibial area (86.04%). The dermal changes seen in MA and LA were almost the same, while the epidermal changes were less frequent in MA. Conclusions: In the present study, most of the patients of macular and LA had clinical and histopathological correlation. There is not much difference in the demographic profile and histopathological characteristics between LA and MA. The findings confirm that the two forms of primary localized cutaneous amyloidosis are closely related variants of one disease. Histological examination will help in confirming the diagnosis.
Keywords: Amyloidosis, lichen amyloidosis, macular amyloidosis
|How to cite this article:|
Thejaswi SR, Rao Shendre ME, Kudligi C, Tophakhane R. A clinicopathological study of primary cutaneous amyloidosis in tertiary care center, Hubballi. Clin Dermatol Rev 2022;6:133-9
|How to cite this URL:|
Thejaswi SR, Rao Shendre ME, Kudligi C, Tophakhane R. A clinicopathological study of primary cutaneous amyloidosis in tertiary care center, Hubballi. Clin Dermatol Rev [serial online] 2022 [cited 2022 Oct 6];6:133-9. Available from: https://www.cdriadvlkn.org/text.asp?2022/6/2/133/354764
| Introduction|| |
Amyloidosis is a generic term, which denotes extracellular deposition of a proteinaceous substance composed of one of a family of biochemically unrelated proteins, depending on the underlying condition, and which is usually associated with considerable tissue dysfunction. Deposits can be localized to a body site or can be systemic, involving several organs and tissues. In primary localized cutaneous amyloidosis, deposition of amyloid occurs in previously apparently normal skin with no evidence of deposits occurring in internal organs.
The term primary cutaneous amyloidosis (PCA) usually includes macular amyloidosis (MA), lichen amyloidosis (LA), and nodular amyloidosis (NA). When LA and MA coexist, the term biphasic amyloidosis (BA) is used. Other variants of PCA include bullous, poikilodermic, vitiliginous, and anosacral types. Macular is the most common and nodular being a rare form.
The pathogenesis, also known as the “keratinocyte-theory,” were the keratinocytes undergo inappropriate apoptosis with filamentous degeneration, which later gets converted into amyloid material. Various risk factors such as female gender, racial factors, exposure to solar radiation, friction/scrub, atopy, and autoimmunity have been observed.
Cutaneous amyloidosis has a varied clinical presentations which are ranging from asymptomatic pigmented macules to waxy translucent nodules, plaques, purpura, and sometimes, bullous lesions. Clinically, it is difficult to distinguish different subtypes of PCA.
In general, the treatment of cutaneous amyloidosis is unsatisfactory. Milder cases can be helped using potent topical corticosteroids. Dermabrasion is beneficial in LA. Other therapeutic modalities tried include antihistamines, etretinate, cyclophosphamide, intralesional injection of corticosteroids, UVB irradiation, and topical dimethylsulphoxide. NA has shown good response to shave removal or curettage.
It is obvious that no one form of therapy is ideal. Hence, it is rare for a patient not to receive several alternative treatments during his or her life. Hence, it is worthwhile to study the various clinical forms and their histopathological features which will help in planning the correct treatment of cutaneous amyloidosis.
| Materials and Methods|| |
This was institution based cross-sectional study conducted on patients of PCA during the period of 18 months from November 2016 to May 2018. All clinically diagnosed cases of cutaneous amyloidosis and who consented for this study were included. Patients having any systemic diseases were excluded from the study. The study was approved by the Ethics Committee of our institution.
The basic data such as age, occupation, and socioeconomic status were recorded. A detailed history regarding the duration of illness, progression, precipitating factors, and family history of similar complaints was also noted. A detailed clinical examination regarding the location of the lesions and type of lesions was done followed by routine blood and urine examination. Patients were subjected to skin biopsy after obtaining a written consent. The biopsy site was cleaned with spirit. After infiltration with 2% lignocaine, an elliptical incision along the skin lines was taken, and a full thickness biopsy of the skin was done. The specimen thus obtained was preserved in 10% formalin and sent to the department of pathology for a detailed histopathological examination. Routine paraffin processing and H and E stain were done. Special stains such as Congo red were done wherever necessary. After obtaining the results, the clinical and histopathological findings were tabulated.
| Results|| |
Among 53,015 new outpatient department (OPD) patients screened for cutaneous amyloidosis [Table 1], 85 (0.16%) patients were recruited who were fullfiling inclusion and exclusion criteria. Out of 85 patients, 37 (43.53%) were males and 48 were females (56.47%). Male-to-female ratio was 1:1.3.
Majority of our patients (60%) belonged to age between 21 and 50 years with 17 patients each in the group of 21–30, 31–40, and 41–50 years, respectively.
Majority of our patients were housewives (38.82%) followed by farmers 16 (18.82%), students 11 (12.94%), clerks and shopkeepers 4 each (4.7%), laborers 3 (3.53%), and teachers 3 (3.53%). Duration of the diseases ranged from 2 months to 30 years, 44 (51.76%) had the duration of the skin lesion between 1 and 5 years, 22 (25.88%) for 6 months to 1 year, 9 (10.58%) for above 10 years, 7 (8.23%) of patients gave duration of 5–10 years, and only 3 (3.52%) of patients gave a history of lesions <6 months.
Pruritis was the presenting symptoms in majority of cases 57 (67.06%), and the rest 28 (32.94%) were asymptomatic.
History of use of scrub was observed in 77 (90.58%) of the patients and the rest 8 (9.4%) had no history of scrub use. Among them, i.e., 59 (76.62%) used only nylon/plastic brush. Five (6.49%) used only pumic stone, 3 (3.90%) used only coconut coir, and the rest 10 (12.99%) used combination of these three [Table 2]. Among them, 58 (68.23%) gave a history of using scrub for more than 10 years, 5 (5.88%) for duration of 6–10 years, and rest 14 patients (16.47%) for 1–5 years [Table 3].
Of 85 patients, only 6 gave positive family history (7.06%); 4 cases of LA and 2 cases of MA had positive family history.
Out of 85 cases, 36 (42.35%) were MA, 43 (50.58%) LA, and 6 (7.05%) were BA. In MA, the most frequently involved area was upper back in 21 (58.33%), of which 8 patients had single site involvement in upper back [Figure 1] and [Figure 2]. LA 24 (55.81%) of them had single site involvement in pretibial area, but overall in LA, the most frequently involved area was pretibial region in 37 (86.04%) [Figure 5], [Figure 6], [Figure 7]. In BA, all six patients had involvement of upper back and pretibial region (100%).
|Figure 1: Macular amyloidosis on upper back region showing rippled pattern|
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Among 43 patients of LA, most frequent epidermal changes were acanthosis 37 (86.04%), hyperkeratosis 36 (83.72%), followed by basal cell pigmentation in 35 (81.39%), papillomatosis in 24 (55.81%), and hypergranulosis in 10 (23.25%) [Table 4].
Dermal changes: amyloid deposits were seen in 40 (93.02) [Figure 8], pigmentory incontinence in 25 (58.14), andlymphohistiocyticinfiltrate in 41 (97.64%) patients of LA
|Figure 8: Histology photograph of patient with lichen amyloidosis with amyloid in papillary dermis (×10)|
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Among 36 patients of MA, most frequent epidermal changes was basal cell pigmentation in 25 (69.45%), followed by hyperkeratosis 23 (63.33%), acanthosis 12 (33.33%), and papillomatosis in 7 (19.44%). Dermal changes and amyloid deposits were seen only in 30 (83.33%), pigmentory incontinence in 20 (55.55%), and lymphohistiocytic infiltrate in all 36 (100%) [Figure 3] and [Figure 4].
|Figure 3: Histopathology photograph of macular amyloidosis showing rounded eosinophillic amyloid in upper papillary dermis(H and E, ×100)|
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|Figure 4: Congo red positive amyloid in upper dermis (Congo Red Stain, ×100)|
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Among 6 patients of BA, acanthosis was seen in all six patients (100%), followed by hyperkeratosis and basal cell pigmentation in 5 each (83.33%), hypergranulosis and papillomatosis in 4 each (66.66%). Dermal changes: all six cases of BA had amyloid (100%), 4 cases had pigmentory incontinence (66.66%), and 6 cases had lymphohistiocytic infiltrate (100%).
| Discussion|| |
Rokintansky gave the first description of amyloidosis in 1842 and the term amyloid (starch like) was originally coined in 1854 by Virchow.,
Amyloidosis can either be localized or systemic. Thevarious forms of localized cutaneous amyloidosis are MA, LA, and NA. Sometimes, the features of LA and MA coincide and are known as biphasicamyloidosis (BA).
The etiopathogenesis of PCA is still unknown. Female gender, racial factors, exposure to sunlight, friction, and atopy have been considered as the possible predisposing/triggering factors. Epidermal keratinocytes undergo filamentous degeneration in 6 stages, resulting in the formation of amyloid was proposed by Kumakiri and Hashimoto. Stage1-fibrillarchanges in the cytoplasm of epidermal keratinocytes, Stage 2 – degeneration of cell organelles and bundle formation bytonofilaments. Stage 3 and 4 comprised filamentouscells and masses, respectively, culminating in the formation of amyloid in Stages 5 and 6.
Yamagehara et al. suggested secretion theory – the amyloid in MA may be secreted by disrupted basal cells which deposits at the dermo-epidermal junction.
In LA and MA, the amyloid is derived from the keratinocytes and hence called K amyloid. Nodularamyloidosis is considered as a cutaneous plasmacytoma, locally producing immunoglobulin light chainsas precursor to AL type fibril proteins, and there is nospecific staining with antikeratin antibodies. Histochemically, early stages of amyloidogenesis did not stain with periodic acid - schiff (PAS), thioflavin T, and Congo red. A dermal component was thoughtto be necessary for full development of amyloid islands withan interaction between macrophages and filamentous massesplaying a role.
Macsween and Saihan and Hashimoto et al. found patients of Asian origin to have a higher rate of the lichen and the macular subtypes than patients of Caucasian origin. Frequent use of nylon cloth for exfoliating skin was suggested to be the likely reason.
During 1½ year of study period, there were 85 new patients with a diagnosis of cutaneous amyloidosis among 53,015 new patients who attended the skin OPD. Hence, the prevalence of cutaneous amyloidosis was 0.16% among the patients attending the skin OPD.
Out of 85 cases of PCA, LA was most common 43 (50.58%), followed by MA 36 (42.35%) and BA6 (7%). In a study by Vijaya et al., LA was the most common variant (65.63%), with MA accounting for only 15.63% and BA seen in 18.75%. A study in Malaysia on PCA showed that only 26% were MA, while 74% were LA. Another study reported that 90% of the cases were MA, while only 10% were LA. A recent study done in south India showed LA as the frequently encountered type (50.5%). These results showed that there could be considerable regional variation in the occurrence which might be due to local cultural practice. Female preponderance with male-to-female ratio being 1:1.3 was oberserved. Similarobservation was seen in other studies.,,,,
The mean age observed in our study is 43.04 years. Moreover, majority of the patients (60%) belonged to age between 21 and 50 years with 17 patients (20% each) in the group of 21–30, 31–40, and 41–50 years, respectively. Similar results were seen in other studies.,,,,,
Majority of our patients were housewives 38.82% followed by farmers 18.82% and students 12.94%. Ourobservation was collaborating with previous studies.,
Duration of the diseases seen in our study ranged from 3 months to 30 years. This correlated with other studies done by Salim et al. Tay and Dacosta, and Al-Ratrout and Satti.
Out of 85 cases 32.94% were asymptomatic and rest 67.06% had pruritus.
Similarly, pruritus as an important complaint was also demonstrated in other studies.,,,,,,,
Positive family history was observed in 7.06% of our patients. Al-Ratrout and Satti and Jayabhanu et al. studies observed similar results. This was significantly low when compared to the other studies done in India.,
Among 85 patients, 77 of the patients gave a history of use of scrub (90.58%) and the rest 8 (9.42%) had no history of scrub use. Similarly, the role of friction in the pathogenesis
Of PCA was observed by Salim et al. Jayabhanu et al. However, in a study done by Biswas et al., patients deny history of chronic friction.
The distribution of lesions in our cases of MA was predominantly seen in the upper back region (63.33%). In the study from Tamil Nadu, Agra, and Delhi, this distribution was 63.3%, 52.63%, and 80%, respectively. The predominant sites of involvement in our patients of LA have been summarized in [Table 5], along with the findings of other studies in this regard. In 6 BA patients, all had involvement of upper back and pretibial region (100%), followed by extensor aspect of forearm 66.66%, extensor aspect of arms 66.66%, and lower back 33.33%.
|Table 5: Predominant sites of involvement in ourpatients of lichen amyloidosis|
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Of all 85 patients, only eight had hypertension and only two had diabetes mellitus which might be casual occurrence not related to amyloidosis. One patient had prurigo nodularis associated with LA. One patient had amyloidosis cutis dyschromica. It is a rare distinct type of PCA characterized by the presence of widespread hypopigmented as well as hyperpigmented macules. 60 year man with asymptomatic skin lesions showing diffuse hyperpigmentation with hypopigmented spots over his whole body but sparing his face, hands, and feet since early childhood. Histopathology of the hyperpigmented lesion revealed increased melanin in the basal layer, pigment incontinence, and amorphous eosinophilic masses stained positive with Congo [Figure 9] red in the papillary dermis. Amyloidosis cutis dyschromica was diagnosed.
|Figure 9: Congo red stain section of lichen amyloidosis with red colored amyloid masses in papillary dermis (×10)|
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Among 36 patients of MA, most frequent epidermal changes were basal cell pigmentation, followed by hyperkeratosis, acanthosis, and papillomatosis. Similar observations were seen in Jayabhanu et al. and Kulkarni et al. Dermal changes such as pigment incontinence, lymphohistiocyticinfilterate, and amyloid were the most common findings observed in MA. Similar observations were found in the study of Jayabhanu et al., Kulkarni et al., Kibbi et al. Al-Ratrout and Satti as well as Black and Jones.
In present study, among 43 patients of LA, most frequent epidermal changes was acanthosis, hyperkeratosis followed by basal cell pigmentation in, papillomatosis and hypergranulosis. Similar observation was seen in Jayabhanu et al. and Kulkarni et al.
Dermal changes in LA 93.02% cases had amyloid deposits, pigmentary incontinence in 58.14%, and lymphohistiocytic infiltrate in 95.34% which is comparable to study done by Kulkarni et al. who reported 93.02% having amyloid deposits, lymphohistiocytic infiltrates in 95.34% of cases. Pigment incontinence was seen 58.14% of the patients. This matches with the study of Salim et al., Kibbi et al.
In BA, acanthosis was seen in all patients (100%), followed by hyperkeratosis and basal cell pigmentation, hypergranulosis, and papillomatosis. Dermal changes were; amyloid was present in 100%, pigmentary incontinence in 66.67%, and lymphohistiocytic infiltrate in 100%. Similar results were observed in Kulkarni et al.
In the present study, out of 85 cases of PCA (MA and LA) in 9 patients (10.59%), amyloid was not detected though these were clinically diagnosed as MA. In these cases, as observed by Black and Jones and Kumar and Dogra, the amyloid deposits can probably be demonstrated by subsequent biopsies. Subsequent biopsies in these patients could not be done because they did not give consent for repeat biopsy.
| Conclusions|| |
We can conclude that PCA is one of the common dermatological and cosmetic problems encountered in middle age population with female preponderance. PCA has varied clinical presentations, LA is most common variant, and followed by MA with most common site involved being pretibial and interscapular region respectively. PCA is often easy to recognize but difficult to treat with unsatisfactory results which may be due to very less understanding of the etiological factors. Majority of our patients gave a history of scrubbing. Though friction might be a causative factor, the habit of scrubbing is a quite common finding in this part of the country. Microscopy in PCA, epidermal changes seen was acanthosis, hyperkeratosis, pigmentation of basal cells, and papillomatosis. The epidermal changes seen in MA were less frequent compared to LA. The dermal changes were amyloid in the papillary dermis, lymphohistiocytic inflammatory infiltrate, and pigment incontinence in both LA and MA. Histopathology in correlation with clinical features and history is required to establish accurate diagnosis which will help in establishing concrete therapy which is lacking. However, further studies are required to find out the genetic, personal, and cultural factors for the disease causation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]