Familial poikylodermic cutaneous amyloidosis

ARTICLE

Auteur(s) : Lourdes Pardo Arranz, Pilar Escalonilla García-Patos, Concepción Román Curto, Susana Blanco Barrios, Emilia Fernández López, Pablo de Unamuno Pérez

Hospital Universitario de Salamanca, Servicio de Dermatología, Paseo de San Vicente 58-132, 37007 Salamanca, Spain

accepté le 4 Février 2008

Primary cutaneous amyloidosis is characterised by a deposition of amyloid in skin with a previously normal aspect, without affecting any other organ. It may present either in its common forms or may appear as one of the uncommon variants. Within the more uncommon forms of primary cutaneous amyloidosis are poikylodermic amyloidosis and familial amyloidosis, among others. A family with several members affected by cutaneous amyloidosis with poikylodermic lesions is presented.

Case report

Skin biopsies taken from both patients revealed amyloid deposits in the papillary dermis, confirmed by staining with crystal violet and Congo red (figures 2A and B). Melanophages and some apoptotic keratinocytes were also observed.

All the explorations carried out, both analytical (haemogram, general biochemistry, determination of thyroid hormones, calcitonin, PTH, ACTH and catecholamines in blood and 24 h urine) and radiological, were normal.

Regarding the family background, both the father (46-years-old) of the two girls and a paternal aunt (51-years-old) [1] had lesions similar to those described. They had also been asymptomatic since adolescence and this had led the father and aunt to seek consultation some years previously. They also displayed a moderate degree of palmo-plantar keratoderma (absent in the sisters) and a thickening of the skin folds in some areas of the tegument. In both (father and aunt) histological studies confirmed the presence of amyloid deposits. Another three family members (the paternal grandfather of the girls and two male cousins (offspring of the aunt)) also had skin lesions, apparently much more discrete, although for family reasons it was not possible to confirm this.

Discussion

Initially, in the case of the poikylodermic form, two clinical modalities were described: 1) the common variant, and 2) the poikyloderma-like cutaneous amyloidosis syndrome [4]. Poikyloderma-like cutaneous amyloidosis proper is characterised by the presence of poikylodermic lesions, lichenoid papules and blisters especially located on the limbs and appearing in adult life (5^th decade). Moreover, in the poikyloderma-like cutaneous amyloidosis syndrome, lesions with the above characteristics also appear, but the affectation is more extended and the clinical features start earlier. In this syndrome other types of alterations are also common, such as photosensitivity, low height and a certain degree of palmo-plantar keratoderma.

More recently, other cases have been published in which the authors have interpreted poikyloderma as a particular form of presentation of macular amyloidosis [5, 6].

In our case, we believe that our patients could be classified within this last variant, since at no time, at least to date, did they have lesions of the lichenoid papule or blister type, and neither did we observe any of the alterations generally associated with the poikyloderma-like cutaneous amyloidosis syndrome. Actually, the aunt of the girls (the first case diagnosed in the family) was studied several years ago [1] and at that time the clinical features were interpreted as being compatible with the mentioned syndrome. This diagnosis was based above all on the early appearance of the disease and on its association with plantar keratoderma. However, the later appearance of the same pathology in her brother and nieces and hence the diagnosis of familial amyloidosis, explains why the lesions appeared early on, as usually occurs in familial cases, unlike sporadic situations. Additionally, the cause of the plantar keratoderma in both the aunt and the girls’ father is not very clear and we do not know whether the girls will develop it at some later date.

In view of poikyloderma-like lesions it is necessary to make a differential diagnosis with other skin diseases, such as vascular atrophic poikyloderma or mycosis fungoides, and also systemic ones such as some connectivopathies or genodermatosis [7].

Although familial forms of primary cutaneous amyloidosis are rare, increasing numbers of cases are being described. In nearly all families with cutaneous amyloidosis this appears in the form of lichen amyloidosis [8] or biphasic amyloidosis [9], also coinciding with the most frequent types in sporadic cases. Most publications reporting family cases have described an autosomal dominant hereditary pattern [10, 11]. In our case, according to the genogram (figure 3) this would also be the mode of transmission of the disease. Nevertheless, other authors have reported a family with cutaneous amyloidosis linked to chromosome X [12]. In this family, females had minimum alterations of their pigmentation whereas in males, as well as the skin affectation being much more pronounced and extended, multiple systemic disturbances were also observed. Another common characteristic in such families is that the lesions tend to appear at earlier ages than in sporadic cases of cutaneous amyloidosis.

A fairly common symptom in primary cutaneous amyloidosis is a more or less intense degree of pruritus, which often precedes the skin lesions [13]. In our case, the lesions were always asymptomatic. Since many studies – exploring different theories – have pointed out the association between familial cutaneous amyloidosis and Sipple’s syndrome or multiple endocrine neoplasia type 2A [14-18], we decided to perform a screening to rule out any alterations in this sense. According to the literature consulted, however, all studies supporting such a relationship coincide in that the deposit of amyloid is located in the back, especially at scapular or interscapular level. In many of these patients and in sporadic cases with the same location, it is believed that the amyloidosis might originate through a mechanism of friction secondary to notalgia paresthetica, a sensorial neuropathy that affects some dorsal nerves [19]. It is also interesting to note that in most of those patients in which both processes coincide, the skin lesions had appeared prior to the diagnosis of the neoplasia and hence some authors [15] advise ruling out MEN-2A in cases of familial cutaneous amyloidosis. In any case we believe that further studies should be conducted with a view to collecting clear and conclusive data about this possible association.

In conclusion, a new family affected by primary cutaneous amyloidosis presenting as poikyloderma is reported. This coexistence has not been described previously in the literature.

Acknowledgements

References

2 Browstein MH, Hashimoto K, Greenwald G. Biphasic amyloidosis. Br J Dermatol 1973; 88: 25-9.

3 Wong CK. Cutaneous amyloidoses. Int J Dermatol 1987; 26(5): 273-7.

4 Ogino A, Tanaka S. Poikiloderma-like cutaneous amyloidosis. Dermatologica 1977; 155: 301-9.

5 Serna-Pérez MJ, Vázquez-Doval FJ, Idoate M, Sola Casas MA, Quintanilla E. Extensive macular amyloidosis associated with poikiloderma. Int J Dermatol 1992; 31: 277-8.

6 Kang HY, Kang WH. Macular amyloidosis presented as poikiloderma: a case report. J Korean Med Sci 2000; 15: 724-6.

7 Ho MH, Chong LY. Poikiloderma-like cutaneous amyloidosis in an ethnic Chinese girl. J Dermatol 1998; 25: 730-4.

8 Hartshorne ST. Familial primary cutaneous amyloidosis en a South African family. Clin Exp Dermatol 1999; 24: 438-42.

9 Vasily DB, Bhatia SG, Uhlin SR. Familial primary cutaneous amyloidosis: clinical, genetic and immunofluorescent studies. Arch Dermatol 1978; 114: 1173-6.

10 Rajagopalan K, Tay CH. Familial lichen amyloidosis: report of 19 cases in 4 generations of a Chinese family in Malaysia. Br J Dermatol 1972; 87: 123-9.

11 Newton JA, Jagjivan A, Bhogal B, McKee PH, McGibbon DH. Familial primary cutaneous amyloidosis. Br J Dermatol 1985; 112: 201-8.

12 Partington MW, Prentice RSA. X-linked cutaneous amyloidosis: further clinical and pathological observations. Am J Med Genet 1989; 32: 115-9.

13 Román C, Herrera E, Armijo M. Amiloidosis cutánea primitiva: a propósito de 13 observaciones. Actas Dermo-Sif 1986; 77(3): 67-74.

14 Seri M, Celli I, Betsos N, Claudiani F, Camera G, Romeo GA. Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis. Clin Genet 1997; 51: 86-90.

15 Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med 1989; 111: 802-6.

16 Nunziata V, di Giovanni G, Lettera AM, D’ Armiento MR, Mancini M. Cutaneous lichen amyloidosis associated with multiple endocrine neoplasia type 2A. Henry Ford Hosp Med J 1989; 37: 144-6.

17 Kousseff BG, Espinoza C, Zamore GA. Sipple syndrome with lichen amyloidosis as a paracrinopathy: pleiotropy, heterogeneity or a contiguous gene? J Am Acad Dermatol 1991; 25: 651-7.

18 Hofstra RMW, Sijmons RH, Stelwagen T, Stulp RP, Kousseff BG, Lips CJM, Steijlen PM, van Voorst Vader PC, Buys CHCM. RET mutation screening in familial cutaneous lichen amyloidosis and in skin amyloidosis associated with multiple endocrine neoplasia. J Invest Derm 1996; 107: 215-8.

19 Robinson MF, Furst EJ, Nunziata V, Brandi ML, Ferrer JP, Bugalho MJGM, di Giovanni G, Smith RJH, Donovan DT, Alford BR, Hejtmancik JF, Colantuoni V, Quadri L, Limbert E, Halperin I, Vilardell E, Gagel RF. Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J 1992; 40: 249-52.