British Journal of Dermatology {\ ^9 2} 127, f)41-f)44.
Diffuse primary cutaneous amyloidosis J.F.BOURKE, J.BERTH-)ONES AND D.A.BURNS Department of Dermatolocfij, l^icesler Roijal Inprmarii, lA'icester Lill iWW.
U.K.
Accepted for publication 22 June 1992
Summary
A case of extensive primary cutaneous amyloidosis exhibiting both macular and lichenoid lesions is reported. Lesions were arranged in a distinctive linear pattern covering much of the trunk and limbs, in places following Blaschko's lines. The coexistence of macular and lichenoid lesions suggests that this is an unusual variant of biphasic cutaneous amyloidosis.
Primary cutaneous amyloidosis is defined as cutaneous amyloidosis in the absence of other systemic or dermatological disease. It may be classified into three principal categories: macular, lichenoid (lichen amyloidosus) and nodular,' The nodular form is rare. It is characterized by the development of single or multiple nodules, most commonly involving the trunk or limbs. It results from a localized plasma cell dyscrasia. Immunohistochemistry of these lesions reveals immunoglobulin light chains,'^ Macular and lichenoid varieties are clinically and histologically distinct from the nodular form, It has been proposed that the amyloid in these varieties arises from degenerate epidermal keratinocytes.' They have characteristic epidemiological profiles and are occasionally inherited.^'' Macular amyloidosis is commoner in Central and South America, India and the Middle East, whereas lichen amyloidosus is more common among the Chinese,' Macular amyloidosis is seen on the limbs and the upper trunk, where hyperpigmented macules 2-3 mm in diameter may coalesce into larger confluent lesions. Lichen amyloidosus develops more commonly on the shins and consists of discrete hyperkeratotic hyperpigmented papules which may coalesce into plaques.
limbs. There were areas of telangiectasia, purpura. scaling and hyperkeratosis. Lichenoid lesions were prominent on the legs. The pattern varied from reticulate over the thighs (Fig. 1) to whorled on the back (Fig. 2) with a well-demarcated linear arrangement over areas
Case report A 46-year-old white Caucasian male presented with a 6-year history of a mildly pruritic rash which first appeared on his right shoulder and subsequently became gradually more widespread. He had no relevant past medical history and there was no family history of any similar condition. Examination revealed a maculopapular, variably pigmented dermatosis involving the trunk and all four Correspondence; DrJ.F.Bourke.
figure 1. Lichenoid lesions in a reticulate pattern on the right thigh.
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Figure 2. Macular lesions in a whorled and arcuate distribution on the back.
Figure 4, liosinophilic amyloid globules in the upper dermis Ihaematoxyiin and eosin x 40).
of the back and upper limbs (Figs. 2 and 3) which appeared to follow Blaschko's lines. Histology revealed round eosinophilic globules in the upper dermis (Fig. 4) which stained positively with Congo red and demonstrated apple-green birefringence when viewed under polarized light. Masses of amyloid fibrils were seen on electron microscopy (Fig, 5), Immunohistochemical staining was negative for kappa and lambda light chains and amyloid A protein, but strongly positive for cytokeratins (Fig. 6), All other investigations (full blood count, biochemical profile, plasma protein electrophoresis. rheumatoid factor, antinuclear factor, creatinine clearance, urine protein excretion and examination for Bence-Jones protein, ECG, chest X-ray, abdominal ultrasound, bone marrow aspirate, rectal biopsy) were normal or negative. There was no evidence of systemic amyloidosis. Over a 3-year follow-up period, the appearance and distribution of the rash have not changed.
Discussion
Figure 3. Linear lesions following Blaschko s lines on the arms.
Our patient presented with both macular and lichenoid lesions coexisting in an extensive and unusual distribution. Extensive variants of macular amyloidosis have been described, and arcuate, swirled or reticulate hyperpigmentation has been documented in some cases. Partington ft al,^ described a family with hereditary cutaneous amyloidosis of variable severity which was very similar in distribution to our case. Individual family members were found to have linear, swirled, streaked or reticulate lesions, sometimes following Blaschko's lines.
DIFFUSE PRIMARY CUTANEOUS AMYLOIDOSIS
643
Figure 5. electron tnicro^copy revealing masses of amyloid Kbrils | x99.(K)()).
Figure 6. Amyloid deposits staining positively for cytokeratin (DakoCKl x40).
However, there were no lichenoid lesions, and the male family members exhibited serious systemic abnormalities {recurrent pneumonia, ulcerative colitis, neurological deficit, urethral stricture, inguinal herniae and amyloid deposition In the cornea). These extracutaneous features and family history were absent in our patient. Zaynoun et al.~ described a 4 i-year-old Syrian man with diffuse macular hyperpigmentation over the face, trunk and limbs. The lesions over the trunk and proximal extremities showed a reticulate and rippled pattern, but not a linear arrangement. Eng et «/.^ described a swirled hypopigmented pattern in twins with macular amyloidosis which resembled the
truncal pattern of hyperpigmentation in our patient, but histology did not reveal amyloid in these areas and the authors attributed the pigmentary change to an independent process. These cases were further complicated by cardiopulmonary anomalies (pulmonary tibrosis, bronchiectasis, and a fibrotic pulmonary valve in one case, and prolonged Q-T interval in the other). Black and Maibach'* described a 17-year-oid Caucasian girl with unilateral hyperpigmented macular amyloidosis affecting the medial aspect of the left thigh, lower leg. ankle, and left lower abdomen. The abdominal component of the eruption was arcuate in appearance but in other areas the macules were poorly defined. No linear or reticulate lesions were present. Extensive cases of lichen amyloidosus have also been reported. Le Boit and Greene'" described symmetrical reticulate abdominal hyperpigmentation in twins with lichen amyloidosus, both of whom had other systemic abnormalities (mental retardation and mitral valve prolapse). Clarke" described a 42-year-old man with extensive lichen amyloidosus involving the forearms, buttocks, thighs and left shin. The lesions, unlike our case, were not arranged in any particular pattern and the syndrome was complicated by granulomatous hepatitis and poor intellect. Our patient differs from these extensive cases of amyloidosis in that he has developed both macular and lichenoid lesions. Another unusual variant of primary cutaneous amyloidosis, so-called poikiloderma-like cutaneous amyloi-
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dosis was originally described by Marchionini and John,'^ and recently reviewed by Ogino and Tanaka.'^ These patients exhibit poikiloderma-like changes, mainly on the extremities, and lichenoid lesions on the shins. Some of these cases also suffered from other disorders and Ogino and Tanaka proposed the existence of a subclass of patients with fight sensitivity, short stature and blister formation or palmoplantar hyperkeratosis (the poikiloderma-like cutaneous amyloidosis syndrome). Although some of the lesions on our patient's body loosely resemble poikiloderma because of the presence of telangiectasia and variable pigmentation, the overall pattern is linear and is distinct from the cases previously described. In addition our patient does not have any of the other systemic features sometimes associated with this form of amyloidosis. Coexistence of macular and lichenoid lesions in cutaneous amyloidosis is well recognized. Brownstein et «/.'•* proposed the title "biphasic primary cutaneous amyloidosis' for these patients, and extensive cases of biphasic amyloidosis have been reported from Thailand. India and Spain.^''"'' Piamphongsant and Kullavanijaya''' described four patients with widespread amyloidosis sparing only the palms and soles. These patients had predominantly macular lesions on the trunk and upper limbs, with lichenoid lesions and guttate hypomelanosis on the shins. Similar cases, but with less extensive involvement, have also been described,'^•^'^ Our case differs in distribution, but not morphology, from those of Piamphongsant and Kullavanijaya and therefore probably represents an extensive variant of biphasic primary cutaneous amyloidosis characterized by a pattern which is in some areas reticulate and in others follows Blaschko's lines. To our knowledge, this clinical picture has not been described previously.
References 1 Breathnach SM, Amyloid and amyloidosis. / Am Acad Dermalol 1988; 18; 1-16, 2 Husby G, Sletten K, Blumenkrantz N, Danlelsen L, Characterization of an amyloid fibril protein from localized amyloidosis of the skin as lambda immunoglobulin light chains of variable subgroup I (A lambda I). CUn Exp Immunol 1S81: 45: 90-6. i Kobayashi H, Hashimoto K. Amyloidogenesis in organ-limited cutaneous amyloidosis: an antigenic identity between epidermal keratin and skin amyloid, / Invest Dermatol 198 J; 80: 66-72. 4 De Pietro WP. Primary familial cutaneous amyloidosis. Arch Dermatal 1981: 117:639-42, 5 Rajagopalan K. Tay CH. I'amilial lichen amyloidosis. Report of 19 cases in 4 generations of a Chinese family in Malaysia, Br / Dermatol 1972: 87: 12 3-9. 6 Partington MW, Marriott P|, Prentice RS et al. Familial cutaneous amyloidosis with systemic manifestations in males. Am / Med Genet 1981: 10: 65-75. 7 Zaynoun S, Erabi M. Kurban A, Macular amyloidosis. Arch Dermatol 1973: 108: 583, 8 Kng AM, Cogan L, (^unnar RM, Blekys I, h'amiliai generalized dyschromic amyloidosis cutis. / Cutan PathnI 1976: 3: 102-8. 9 Black MM, Maibach HI. Macular amyloidosis simulating naevoid hyperpigmentation, Br J Dermatol 1974; 90: 461-4. 10 I-e Boit PE, Greene I, Primary cutaneous amyloidosis; identically distributed lesions in identical twins. Pediatr Dermatol 1986; 3: 244-6, 11 Clarke [. Widespread lichen amyloidosus. / R ,SW Med 1979: 72: 61-2. 12 Marchionini A, )ohn [•", tlber lichcnoide und poikilodermieartige Hautamyloidose, Arch f Dermal u Sijph 173: 545-61. 1 3 Ogino A, Tanaka S. Poikiloderma-tike cutaneous amyloidosis. Dermatolofjica 1977; 155: 301-9. 14 Brownstein MH, Hashimoto K, Greenwald G, Biphasic amyloidosis: link between macular and iichenoid forms. BrJDermatol 1973: 88: 25-9. 1 5 Piamphongsant T, Kullavanijaya P. Diffuse biphasic amyloidosis. Dermatologica 1976; 153: 243-8. 16 Bedi TR, Datta BN, Diffuse biphasic cutaneous amyloidosis, l>rmatolo!iica 1979: 158:43 3-7. 1 7 Toribio |, Ouifiones PA, Virgil TR, Santa-Cruz CS, Mixed Ilichenoid and macular) cutaneous amyloidoses. Acta Derm Venereol (Stockh) 1975: 55:221-6.
Diffuse primary cutaneous amyloidosis J.F.BOURKE, J.BERTH-)ONES AND D.A.BURNS Department of Dermatolocfij, l^icesler Roijal Inprmarii, lA'icester Lill iWW.
U.K.
Accepted for publication 22 June 1992
Summary
A case of extensive primary cutaneous amyloidosis exhibiting both macular and lichenoid lesions is reported. Lesions were arranged in a distinctive linear pattern covering much of the trunk and limbs, in places following Blaschko's lines. The coexistence of macular and lichenoid lesions suggests that this is an unusual variant of biphasic cutaneous amyloidosis.
Primary cutaneous amyloidosis is defined as cutaneous amyloidosis in the absence of other systemic or dermatological disease. It may be classified into three principal categories: macular, lichenoid (lichen amyloidosus) and nodular,' The nodular form is rare. It is characterized by the development of single or multiple nodules, most commonly involving the trunk or limbs. It results from a localized plasma cell dyscrasia. Immunohistochemistry of these lesions reveals immunoglobulin light chains,'^ Macular and lichenoid varieties are clinically and histologically distinct from the nodular form, It has been proposed that the amyloid in these varieties arises from degenerate epidermal keratinocytes.' They have characteristic epidemiological profiles and are occasionally inherited.^'' Macular amyloidosis is commoner in Central and South America, India and the Middle East, whereas lichen amyloidosus is more common among the Chinese,' Macular amyloidosis is seen on the limbs and the upper trunk, where hyperpigmented macules 2-3 mm in diameter may coalesce into larger confluent lesions. Lichen amyloidosus develops more commonly on the shins and consists of discrete hyperkeratotic hyperpigmented papules which may coalesce into plaques.
limbs. There were areas of telangiectasia, purpura. scaling and hyperkeratosis. Lichenoid lesions were prominent on the legs. The pattern varied from reticulate over the thighs (Fig. 1) to whorled on the back (Fig. 2) with a well-demarcated linear arrangement over areas
Case report A 46-year-old white Caucasian male presented with a 6-year history of a mildly pruritic rash which first appeared on his right shoulder and subsequently became gradually more widespread. He had no relevant past medical history and there was no family history of any similar condition. Examination revealed a maculopapular, variably pigmented dermatosis involving the trunk and all four Correspondence; DrJ.F.Bourke.
figure 1. Lichenoid lesions in a reticulate pattern on the right thigh.
641
642
J.F.BOURKE et al.
Figure 2. Macular lesions in a whorled and arcuate distribution on the back.
Figure 4, liosinophilic amyloid globules in the upper dermis Ihaematoxyiin and eosin x 40).
of the back and upper limbs (Figs. 2 and 3) which appeared to follow Blaschko's lines. Histology revealed round eosinophilic globules in the upper dermis (Fig. 4) which stained positively with Congo red and demonstrated apple-green birefringence when viewed under polarized light. Masses of amyloid fibrils were seen on electron microscopy (Fig, 5), Immunohistochemical staining was negative for kappa and lambda light chains and amyloid A protein, but strongly positive for cytokeratins (Fig. 6), All other investigations (full blood count, biochemical profile, plasma protein electrophoresis. rheumatoid factor, antinuclear factor, creatinine clearance, urine protein excretion and examination for Bence-Jones protein, ECG, chest X-ray, abdominal ultrasound, bone marrow aspirate, rectal biopsy) were normal or negative. There was no evidence of systemic amyloidosis. Over a 3-year follow-up period, the appearance and distribution of the rash have not changed.
Discussion
Figure 3. Linear lesions following Blaschko s lines on the arms.
Our patient presented with both macular and lichenoid lesions coexisting in an extensive and unusual distribution. Extensive variants of macular amyloidosis have been described, and arcuate, swirled or reticulate hyperpigmentation has been documented in some cases. Partington ft al,^ described a family with hereditary cutaneous amyloidosis of variable severity which was very similar in distribution to our case. Individual family members were found to have linear, swirled, streaked or reticulate lesions, sometimes following Blaschko's lines.
DIFFUSE PRIMARY CUTANEOUS AMYLOIDOSIS
643
Figure 5. electron tnicro^copy revealing masses of amyloid Kbrils | x99.(K)()).
Figure 6. Amyloid deposits staining positively for cytokeratin (DakoCKl x40).
However, there were no lichenoid lesions, and the male family members exhibited serious systemic abnormalities {recurrent pneumonia, ulcerative colitis, neurological deficit, urethral stricture, inguinal herniae and amyloid deposition In the cornea). These extracutaneous features and family history were absent in our patient. Zaynoun et al.~ described a 4 i-year-old Syrian man with diffuse macular hyperpigmentation over the face, trunk and limbs. The lesions over the trunk and proximal extremities showed a reticulate and rippled pattern, but not a linear arrangement. Eng et «/.^ described a swirled hypopigmented pattern in twins with macular amyloidosis which resembled the
truncal pattern of hyperpigmentation in our patient, but histology did not reveal amyloid in these areas and the authors attributed the pigmentary change to an independent process. These cases were further complicated by cardiopulmonary anomalies (pulmonary tibrosis, bronchiectasis, and a fibrotic pulmonary valve in one case, and prolonged Q-T interval in the other). Black and Maibach'* described a 17-year-oid Caucasian girl with unilateral hyperpigmented macular amyloidosis affecting the medial aspect of the left thigh, lower leg. ankle, and left lower abdomen. The abdominal component of the eruption was arcuate in appearance but in other areas the macules were poorly defined. No linear or reticulate lesions were present. Extensive cases of lichen amyloidosus have also been reported. Le Boit and Greene'" described symmetrical reticulate abdominal hyperpigmentation in twins with lichen amyloidosus, both of whom had other systemic abnormalities (mental retardation and mitral valve prolapse). Clarke" described a 42-year-old man with extensive lichen amyloidosus involving the forearms, buttocks, thighs and left shin. The lesions, unlike our case, were not arranged in any particular pattern and the syndrome was complicated by granulomatous hepatitis and poor intellect. Our patient differs from these extensive cases of amyloidosis in that he has developed both macular and lichenoid lesions. Another unusual variant of primary cutaneous amyloidosis, so-called poikiloderma-like cutaneous amyloi-
644
J.F.BOURKE et al
dosis was originally described by Marchionini and John,'^ and recently reviewed by Ogino and Tanaka.'^ These patients exhibit poikiloderma-like changes, mainly on the extremities, and lichenoid lesions on the shins. Some of these cases also suffered from other disorders and Ogino and Tanaka proposed the existence of a subclass of patients with fight sensitivity, short stature and blister formation or palmoplantar hyperkeratosis (the poikiloderma-like cutaneous amyloidosis syndrome). Although some of the lesions on our patient's body loosely resemble poikiloderma because of the presence of telangiectasia and variable pigmentation, the overall pattern is linear and is distinct from the cases previously described. In addition our patient does not have any of the other systemic features sometimes associated with this form of amyloidosis. Coexistence of macular and lichenoid lesions in cutaneous amyloidosis is well recognized. Brownstein et «/.'•* proposed the title "biphasic primary cutaneous amyloidosis' for these patients, and extensive cases of biphasic amyloidosis have been reported from Thailand. India and Spain.^''"'' Piamphongsant and Kullavanijaya''' described four patients with widespread amyloidosis sparing only the palms and soles. These patients had predominantly macular lesions on the trunk and upper limbs, with lichenoid lesions and guttate hypomelanosis on the shins. Similar cases, but with less extensive involvement, have also been described,'^•^'^ Our case differs in distribution, but not morphology, from those of Piamphongsant and Kullavanijaya and therefore probably represents an extensive variant of biphasic primary cutaneous amyloidosis characterized by a pattern which is in some areas reticulate and in others follows Blaschko's lines. To our knowledge, this clinical picture has not been described previously.
References 1 Breathnach SM, Amyloid and amyloidosis. / Am Acad Dermalol 1988; 18; 1-16, 2 Husby G, Sletten K, Blumenkrantz N, Danlelsen L, Characterization of an amyloid fibril protein from localized amyloidosis of the skin as lambda immunoglobulin light chains of variable subgroup I (A lambda I). CUn Exp Immunol 1S81: 45: 90-6. i Kobayashi H, Hashimoto K. Amyloidogenesis in organ-limited cutaneous amyloidosis: an antigenic identity between epidermal keratin and skin amyloid, / Invest Dermatol 198 J; 80: 66-72. 4 De Pietro WP. Primary familial cutaneous amyloidosis. Arch Dermatal 1981: 117:639-42, 5 Rajagopalan K. Tay CH. I'amilial lichen amyloidosis. Report of 19 cases in 4 generations of a Chinese family in Malaysia, Br / Dermatol 1972: 87: 12 3-9. 6 Partington MW, Marriott P|, Prentice RS et al. Familial cutaneous amyloidosis with systemic manifestations in males. Am / Med Genet 1981: 10: 65-75. 7 Zaynoun S, Erabi M. Kurban A, Macular amyloidosis. Arch Dermatol 1973: 108: 583, 8 Kng AM, Cogan L, (^unnar RM, Blekys I, h'amiliai generalized dyschromic amyloidosis cutis. / Cutan PathnI 1976: 3: 102-8. 9 Black MM, Maibach HI. Macular amyloidosis simulating naevoid hyperpigmentation, Br J Dermatol 1974; 90: 461-4. 10 I-e Boit PE, Greene I, Primary cutaneous amyloidosis; identically distributed lesions in identical twins. Pediatr Dermatol 1986; 3: 244-6, 11 Clarke [. Widespread lichen amyloidosus. / R ,SW Med 1979: 72: 61-2. 12 Marchionini A, )ohn [•", tlber lichcnoide und poikilodermieartige Hautamyloidose, Arch f Dermal u Sijph 173: 545-61. 1 3 Ogino A, Tanaka S. Poikiloderma-tike cutaneous amyloidosis. Dermatolofjica 1977; 155: 301-9. 14 Brownstein MH, Hashimoto K, Greenwald G, Biphasic amyloidosis: link between macular and iichenoid forms. BrJDermatol 1973: 88: 25-9. 1 5 Piamphongsant T, Kullavanijaya P. Diffuse biphasic amyloidosis. Dermatologica 1976; 153: 243-8. 16 Bedi TR, Datta BN, Diffuse biphasic cutaneous amyloidosis, l>rmatolo!iica 1979: 158:43 3-7. 1 7 Toribio |, Ouifiones PA, Virgil TR, Santa-Cruz CS, Mixed Ilichenoid and macular) cutaneous amyloidoses. Acta Derm Venereol (Stockh) 1975: 55:221-6.
