Clinical dermatology • Concise report
CED
Clinical and Experimental Dermatology
Primary cutaneous nodular amyloidosis associated with psoriasis C. Y. Ung,1 N. J. Carr2 and M. R. Ardern-Jones1,3 Departments of 1Dermatology and 2Pathology, University Hospitals Southampton NHS Foundation Trust, Southampton, UK; and 3Faculty of Medicine, University of Southampton, Southampton, UK doi:10.1111/ced.12347
Summary
Primary cutaneous nodular amyloidosis (PCNA) presents as solitary or multiple firm, waxy nodules with a predilection for acral areas. Histologically, PCNA can be identical to myeloma-associated systemic amyloidosis with monoclonal immunoglobulin light chain deposits. We describe a patient in whom PCNA developed in a scar in an area affected by chronic plaque psoriasis. PCNA has previously been associated with other autoimmune diseases, but to our knowledge, this is the first association with psoriasis. Interestingly, T helper (Th)17 cells, which are crucial in psoriasis pathogenesis, have recently been implicated in promotion of myeloma and plasma cell dyscrasias. The association of psoriasis and plasma-cell light chain production in the skin, as in this case, suggests a possible role for Th17 cells in PCNA formation. The dermatopathological literature of this rare but important disease is discussed.
Cutaneous amyloidosis can occur as a primary cutaneous form in the absence of other organ involvement, or as part of systemic disease with secondary cutaneous involvement. Primary cutaneous nodular amyloidosis (PCNA) is the rarest form of cutaneous amyloidosis. As with primary systemic amyloidosis, it is associated with monoclonal immunoglobulin light chain infiltrates. It is thought to arise from skininfiltrating plasma cells, which typically surround the lesion. We report a patient with active psoriasis who developed plasma cell-poor PCNA in a longstanding traumatic scar.
Report A 29-year-old woman presented with a 5-year history of a lump arising in a scar on her right shin, which had been slowly enlarging without symptoms. She recalled a deep wound at the same site following a Correspondence: Dr Michael Ardern-Jones, Department of Dermatology, Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 11 January 2014
608
Clinical and Experimental Dermatology (2014) 39, pp608–611
kick from a horse at the age of 10 years. She had plaque psoriasis, which had been present since the age of 16 years, and chronically affected her shins and other sites; this had become worse over the preceding 7 years. Topical treatments had included corticosteroids, vitamin D analogues and coal tar/salicylic acid formulations, and she had previously required treatment with phototherapy. Physical examination of the lump revealed a firm purple nodule, 12 9 10 mm in size, on the patient’s medial right shin (Fig. 1). The differential diagnoses included a foreign body granuloma, dermatofibroma and malignant soft tissue tumours. The lesion was fully excised. Histological examination showed an extensive dense collection of amorphous hyaline eosinophilic material in the dermis, substantially replacing normal architecture. There were numerous giant cells, but plasma cells were few in number (Fig. 2). Congo red staining was strongly positive, and exhibited apple-green birefringence when viewed under high-intensity crosspolarized light (Fig. 3). Immunohistochemistry was positive for amyloid P component. Staining with specific monoclonal antibodies demonstrated reactivity to lambda light chains (staining was negative for kappa light chains and amyloid A).
ª 2014 British Association of Dermatologists
PCNA associated with psoriasis C. Y. Ung et al.
Table 1 Investigations required for primary cutaneous nodular amyloidosis, and results in our case.
Figure 1 Nodule on the anterior right shin.
Investigation
Result
Full blood count, sedimentation rate Metabolic panel (liver function, renal function, electrolytes, calcium, glucose) Urinalysis Serum and urine protein electrophoresis Serum immunoglobulin level Serum free light chain assay Imaging (chest radiography, abdominal ultrasonography scan, echocardiography, electrocardiogram) Bone marrow biopsy
Normal Normal
Serum amyloid P scintigraphy
Normal Normal Normal Normal Normal
No evidence of plasma cell dyscrasia, and no evidence of light chain (AL) amyloid No visceral uptake
Figure 2 The dermis was expanded by nodular deposits of
amyloid, which stained pale pink (haematoxylin and eosin, original magnification 9 2). Figure 3 The amyloid deposits were positive for Congo red
All laboratory investigations were normal (Table 1). A diagnosis of PCNA was made. Clinically, PNCA is characterized by solitary or multiple firm, waxy nodules or infiltrated plaques, ranging from millimetres to centimetres in size, with or without overlying atrophic epidermis. The commonest affected areas are the legs, face and trunk. Hyaline eosinophilic material in the skin may mimic amyloid histologically, and is recognized in a number of diseases including colloid milium, cutaneous porphyria, lipoid proteinosis and Waldenstrom macroglobulinaemia (Table 2). The majority of primary cutaneous amyloidoses are derived from apoptosis of keratinocytes, typically releasing cytokeratin-5 (amyloid keratin; AK amyloid), but other proteins such as apolipoprotein E4 (ApoE4
ª 2014 British Association of Dermatologists
(original magnification 9 10).
amyloid) have also been identified. Such keratinic amyloidoses (AK amyloid) typically present as lichen amyloid or macular amyloid. The presence of AK amyloid can often be detected in association with skin tumours (e.g. basal cell carcinoma, squamous cell carcinoma, appendageal tumours) and in other situations (e.g. seborrhoeic keratosis, solar elastosis, discoid lupus). However, in our case, the amyloid protein was derived from immunoglobulin light chain production. Systemic disease causing cutaneous amyloid deposits are most commonly related to coexistent inflammatory or neoplastic disease inducing serum amyloid A proteins (SAA amyloid), which are a family of apolipoproteins synthesized predominantly by the liver,
Clinical and Experimental Dermatology (2014) 39, pp608–611
609
PCNA associated with psoriasis C. Y. Ung et al.
Table 2 Other conditions with cutaneous hyaline deposits. Histological features Colloid milium
Cutaneous porphyrias
Lipoid proteinosis
€m macroglobulinaemia Waldenstro
Eosinophilic deposits in the upper dermis. The deposits have been reported to stain positively with Congo red and diastase–PAS on occasion. Ultrastructurally, the deposits consist of delicate branching wavy filaments, unlike the straight nonbranching filaments of amyloid Eosinophilic deposits in the epidermal basement membrane and upper dermal blood vessels. The deposits are diastase–PAS positive and can also express serum amyloid P. Electron microscopy reveals multiplication of basement membrane material Eosinophilic deposits in and around dermal capillaries, later spreading to the lower dermis and surrounding adnexal structures. The deposits are diastase–PAS positive. Ultrastructurally, collagen fibrils are surrounded by an amorphous granular matrix, and there is basal lamina reduplication around blood vessels Deposition of hyaline material in the upper dermis composed of monoclonal IgM The deposits are positive for diastase–PAS but negative for Congo red
PAS, periodic-acid–Schiff.
especially during inflammation (e.g. rheumatoid arthritis, bronchiectasis, Hodgkin disease). Other amyloid variants may be hereditary and affect specific proteins (e.g. hereditary transthyretin amyloidosis, hereditary cystatin C amyloidosis). A further source of amyloid protein arises in monoclonal plasma cell dyscrasias, producing immunoglobulin light chains as amyloid precursors: light-chain (AL) amyloid (as found in multiple myeloma, Waldenstr€ om disease and lymphomas). In our case, there was extensive AL amyloid infiltration in the dermis, subcutis and blood vessel wall. This pattern is indistinguishable from that found in primary and myeloma-associated systemic amyloidosis. Thus, systemic involvement must be excluded in patients presenting with nodular amyloidosis. Cutaneous AL amyloid deposits identified in the absence of systemic disease are very rare.1,2 Nevertheless, although cases of PCNA have been reported to precede paraproteinaemia and systemic amyloidosis, the risk was shown to be approximately 7% in a series of 15 cases followed up for an average of 12.3 6.8 years.3 Following careful observation including serum amyloid P (SAP) scintigraphy, our patient remained well after 3 years of follow-up, and will be re-screened at 5 years for systemic amyloidosis. PCNA associations with Sj€ ogren syndrome, CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly, telangiectasia) syndrome and diabetes mellitus have been described,2 but to our knowledge, this is the first case identified in association with active psoriasis in the same body site. Interestingly, an extensive plasma cell infiltrate was not observed in our case. Instead, a significant histiocytic component was identified. Plasma cell-rich and
610
Clinical and Experimental Dermatology (2014) 39, pp608–611
plasma cell-poor variants of PCNA raise the possibility that these two histological subtypes represent different conditions. It is our opinion that they are recognized by skin pathologists, but are under-reported in the dermatopathological literature. In our case, the finding of AL amyloid lambda with no AL amyloid kappa and a relative paucity of plasma cells, despite a large nodule comprised of immunoglobulin light chains, suggests to us that the causative plasma cell population is longlived and clonal. Although local trauma has rarely been reported to precede development of PCNA,4,5 it is not clear if any of these few cases had coexistent psoriasis. It seems possible that foreign material persisting in the soft tissues from the original injury could act as an antigenic target for B-cell antibody production. However, foreign body reactions in the skin are well recognized and typically show a granulomatous response. Macrophage activation leading to granuloma formation is thought to be dominantly regulated by interferon-c production from T helper (Th)1 cells, and an increased risk of foreign body granulomas is seen in sarcoidosis (e.g. with tattoos) which is considered to be primarily a Th1 disease. However, in psoriatic inflammation, granulomas are not a feature, and the contrasting immunopathology of interleukin-17 production by Th17 cells is central to the pathogenesis.6 Furthermore, Th17 cells have recently been shown to play an important role in the promotion of plasma cell dyscrasia and myeloma,7,8 and monoclonal gammopathy has been shown to arise more frequently in patients with psoriasis and psoriatic arthritis.9,10 Taken together, these findings suggest the possibility that in this case, the milieu of psoriatic skin switched a ‘normal’ granulomatous foreign body response to an abnormal Th17-driven stimulus for
ª 2014 British Association of Dermatologists
PCNA associated with psoriasis C. Y. Ung et al.
B-cell activation. Thus we speculate that the immunological profile of psoriasis may have contributed to the development of PCNA in this case.
Learning points ● Amyloid protein is most commonly derived
from aberrant production of apolipoprotein and cytokeratin; immunoglobulin light chain amyloid is less common. ● PCNA can display identical pathological features to myeloma-associated systemic amyloidosis. ● Patients with a confirmed diagnosis of PCNA need systemic evaluation and long-term followup. ● Psoriasis is associated with an increased risk of plasma cell dyscrasias, and this report suggests a possible association with PCNA. ● Hyaline eosinophilic deposits in colloid milium, lipoid proteinosis, the porphyrias and Waldenstrom macroglobulinaemia can mimic amyloid histologically.
References 1 Fernandez-Flores A. Cutaneous amyloidosis: a concept review. Am J Dermatopathol 2012; 34: 1–14; quiz 15–17.
ª 2014 British Association of Dermatologists
2 Schreml S, Szeimies RM, Vogt T et al. Cutaneous amyloidosis and systemic amyloidoses with cutaneous involvement. Eur J Dermatol 2010; 20: 152– 60. 3 Woollons A, Black MM. Nodular localized primary cutaneous amyloidosis: a long-term follow-up study. Br J Dermatol 2001; 145: 105–9. 4 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. 5 Lee DY, Kim YJ, Lee JY et al. Primary localized cutaneous nodular amyloidosis following local trauma. Ann Dermatol 2011; 23: 515–18. 6 Elloso MM, Gomez-Angelats M, Fourie AM. Targeting the Th17 pathway in psoriasis. J Leukoc Biol 2012; 92: 1187–97. 7 Prabhala RH, Pelluru D, Fulciniti M et al. Elevated IL-17 produced by Th17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010; 115: 5385–92. 8 Noonan K, Marchionni L, Anderson J et al. A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 2010; 116: 3554–63. 9 Wittenberg GP, Oursler JR, Peters MS. Secondary amyloidosis complicating psoriasis. J Am Acad Dermatol 1995; 32: 465–8. 10 Eder L, Thavaneswaran A, Pereira D et al. Prevalence of monoclonal gammopathy among patients with psoriatic arthritis. J Rheumatol 2012; 39: 564–7.
Clinical and Experimental Dermatology (2014) 39, pp608–611
611
CED
Clinical and Experimental Dermatology
Primary cutaneous nodular amyloidosis associated with psoriasis C. Y. Ung,1 N. J. Carr2 and M. R. Ardern-Jones1,3 Departments of 1Dermatology and 2Pathology, University Hospitals Southampton NHS Foundation Trust, Southampton, UK; and 3Faculty of Medicine, University of Southampton, Southampton, UK doi:10.1111/ced.12347
Summary
Primary cutaneous nodular amyloidosis (PCNA) presents as solitary or multiple firm, waxy nodules with a predilection for acral areas. Histologically, PCNA can be identical to myeloma-associated systemic amyloidosis with monoclonal immunoglobulin light chain deposits. We describe a patient in whom PCNA developed in a scar in an area affected by chronic plaque psoriasis. PCNA has previously been associated with other autoimmune diseases, but to our knowledge, this is the first association with psoriasis. Interestingly, T helper (Th)17 cells, which are crucial in psoriasis pathogenesis, have recently been implicated in promotion of myeloma and plasma cell dyscrasias. The association of psoriasis and plasma-cell light chain production in the skin, as in this case, suggests a possible role for Th17 cells in PCNA formation. The dermatopathological literature of this rare but important disease is discussed.
Cutaneous amyloidosis can occur as a primary cutaneous form in the absence of other organ involvement, or as part of systemic disease with secondary cutaneous involvement. Primary cutaneous nodular amyloidosis (PCNA) is the rarest form of cutaneous amyloidosis. As with primary systemic amyloidosis, it is associated with monoclonal immunoglobulin light chain infiltrates. It is thought to arise from skininfiltrating plasma cells, which typically surround the lesion. We report a patient with active psoriasis who developed plasma cell-poor PCNA in a longstanding traumatic scar.
Report A 29-year-old woman presented with a 5-year history of a lump arising in a scar on her right shin, which had been slowly enlarging without symptoms. She recalled a deep wound at the same site following a Correspondence: Dr Michael Ardern-Jones, Department of Dermatology, Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 11 January 2014
608
Clinical and Experimental Dermatology (2014) 39, pp608–611
kick from a horse at the age of 10 years. She had plaque psoriasis, which had been present since the age of 16 years, and chronically affected her shins and other sites; this had become worse over the preceding 7 years. Topical treatments had included corticosteroids, vitamin D analogues and coal tar/salicylic acid formulations, and she had previously required treatment with phototherapy. Physical examination of the lump revealed a firm purple nodule, 12 9 10 mm in size, on the patient’s medial right shin (Fig. 1). The differential diagnoses included a foreign body granuloma, dermatofibroma and malignant soft tissue tumours. The lesion was fully excised. Histological examination showed an extensive dense collection of amorphous hyaline eosinophilic material in the dermis, substantially replacing normal architecture. There were numerous giant cells, but plasma cells were few in number (Fig. 2). Congo red staining was strongly positive, and exhibited apple-green birefringence when viewed under high-intensity crosspolarized light (Fig. 3). Immunohistochemistry was positive for amyloid P component. Staining with specific monoclonal antibodies demonstrated reactivity to lambda light chains (staining was negative for kappa light chains and amyloid A).
ª 2014 British Association of Dermatologists
PCNA associated with psoriasis C. Y. Ung et al.
Table 1 Investigations required for primary cutaneous nodular amyloidosis, and results in our case.
Figure 1 Nodule on the anterior right shin.
Investigation
Result
Full blood count, sedimentation rate Metabolic panel (liver function, renal function, electrolytes, calcium, glucose) Urinalysis Serum and urine protein electrophoresis Serum immunoglobulin level Serum free light chain assay Imaging (chest radiography, abdominal ultrasonography scan, echocardiography, electrocardiogram) Bone marrow biopsy
Normal Normal
Serum amyloid P scintigraphy
Normal Normal Normal Normal Normal
No evidence of plasma cell dyscrasia, and no evidence of light chain (AL) amyloid No visceral uptake
Figure 2 The dermis was expanded by nodular deposits of
amyloid, which stained pale pink (haematoxylin and eosin, original magnification 9 2). Figure 3 The amyloid deposits were positive for Congo red
All laboratory investigations were normal (Table 1). A diagnosis of PCNA was made. Clinically, PNCA is characterized by solitary or multiple firm, waxy nodules or infiltrated plaques, ranging from millimetres to centimetres in size, with or without overlying atrophic epidermis. The commonest affected areas are the legs, face and trunk. Hyaline eosinophilic material in the skin may mimic amyloid histologically, and is recognized in a number of diseases including colloid milium, cutaneous porphyria, lipoid proteinosis and Waldenstrom macroglobulinaemia (Table 2). The majority of primary cutaneous amyloidoses are derived from apoptosis of keratinocytes, typically releasing cytokeratin-5 (amyloid keratin; AK amyloid), but other proteins such as apolipoprotein E4 (ApoE4
ª 2014 British Association of Dermatologists
(original magnification 9 10).
amyloid) have also been identified. Such keratinic amyloidoses (AK amyloid) typically present as lichen amyloid or macular amyloid. The presence of AK amyloid can often be detected in association with skin tumours (e.g. basal cell carcinoma, squamous cell carcinoma, appendageal tumours) and in other situations (e.g. seborrhoeic keratosis, solar elastosis, discoid lupus). However, in our case, the amyloid protein was derived from immunoglobulin light chain production. Systemic disease causing cutaneous amyloid deposits are most commonly related to coexistent inflammatory or neoplastic disease inducing serum amyloid A proteins (SAA amyloid), which are a family of apolipoproteins synthesized predominantly by the liver,
Clinical and Experimental Dermatology (2014) 39, pp608–611
609
PCNA associated with psoriasis C. Y. Ung et al.
Table 2 Other conditions with cutaneous hyaline deposits. Histological features Colloid milium
Cutaneous porphyrias
Lipoid proteinosis
€m macroglobulinaemia Waldenstro
Eosinophilic deposits in the upper dermis. The deposits have been reported to stain positively with Congo red and diastase–PAS on occasion. Ultrastructurally, the deposits consist of delicate branching wavy filaments, unlike the straight nonbranching filaments of amyloid Eosinophilic deposits in the epidermal basement membrane and upper dermal blood vessels. The deposits are diastase–PAS positive and can also express serum amyloid P. Electron microscopy reveals multiplication of basement membrane material Eosinophilic deposits in and around dermal capillaries, later spreading to the lower dermis and surrounding adnexal structures. The deposits are diastase–PAS positive. Ultrastructurally, collagen fibrils are surrounded by an amorphous granular matrix, and there is basal lamina reduplication around blood vessels Deposition of hyaline material in the upper dermis composed of monoclonal IgM The deposits are positive for diastase–PAS but negative for Congo red
PAS, periodic-acid–Schiff.
especially during inflammation (e.g. rheumatoid arthritis, bronchiectasis, Hodgkin disease). Other amyloid variants may be hereditary and affect specific proteins (e.g. hereditary transthyretin amyloidosis, hereditary cystatin C amyloidosis). A further source of amyloid protein arises in monoclonal plasma cell dyscrasias, producing immunoglobulin light chains as amyloid precursors: light-chain (AL) amyloid (as found in multiple myeloma, Waldenstr€ om disease and lymphomas). In our case, there was extensive AL amyloid infiltration in the dermis, subcutis and blood vessel wall. This pattern is indistinguishable from that found in primary and myeloma-associated systemic amyloidosis. Thus, systemic involvement must be excluded in patients presenting with nodular amyloidosis. Cutaneous AL amyloid deposits identified in the absence of systemic disease are very rare.1,2 Nevertheless, although cases of PCNA have been reported to precede paraproteinaemia and systemic amyloidosis, the risk was shown to be approximately 7% in a series of 15 cases followed up for an average of 12.3 6.8 years.3 Following careful observation including serum amyloid P (SAP) scintigraphy, our patient remained well after 3 years of follow-up, and will be re-screened at 5 years for systemic amyloidosis. PCNA associations with Sj€ ogren syndrome, CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly, telangiectasia) syndrome and diabetes mellitus have been described,2 but to our knowledge, this is the first case identified in association with active psoriasis in the same body site. Interestingly, an extensive plasma cell infiltrate was not observed in our case. Instead, a significant histiocytic component was identified. Plasma cell-rich and
610
Clinical and Experimental Dermatology (2014) 39, pp608–611
plasma cell-poor variants of PCNA raise the possibility that these two histological subtypes represent different conditions. It is our opinion that they are recognized by skin pathologists, but are under-reported in the dermatopathological literature. In our case, the finding of AL amyloid lambda with no AL amyloid kappa and a relative paucity of plasma cells, despite a large nodule comprised of immunoglobulin light chains, suggests to us that the causative plasma cell population is longlived and clonal. Although local trauma has rarely been reported to precede development of PCNA,4,5 it is not clear if any of these few cases had coexistent psoriasis. It seems possible that foreign material persisting in the soft tissues from the original injury could act as an antigenic target for B-cell antibody production. However, foreign body reactions in the skin are well recognized and typically show a granulomatous response. Macrophage activation leading to granuloma formation is thought to be dominantly regulated by interferon-c production from T helper (Th)1 cells, and an increased risk of foreign body granulomas is seen in sarcoidosis (e.g. with tattoos) which is considered to be primarily a Th1 disease. However, in psoriatic inflammation, granulomas are not a feature, and the contrasting immunopathology of interleukin-17 production by Th17 cells is central to the pathogenesis.6 Furthermore, Th17 cells have recently been shown to play an important role in the promotion of plasma cell dyscrasia and myeloma,7,8 and monoclonal gammopathy has been shown to arise more frequently in patients with psoriasis and psoriatic arthritis.9,10 Taken together, these findings suggest the possibility that in this case, the milieu of psoriatic skin switched a ‘normal’ granulomatous foreign body response to an abnormal Th17-driven stimulus for
ª 2014 British Association of Dermatologists
PCNA associated with psoriasis C. Y. Ung et al.
B-cell activation. Thus we speculate that the immunological profile of psoriasis may have contributed to the development of PCNA in this case.
Learning points ● Amyloid protein is most commonly derived
from aberrant production of apolipoprotein and cytokeratin; immunoglobulin light chain amyloid is less common. ● PCNA can display identical pathological features to myeloma-associated systemic amyloidosis. ● Patients with a confirmed diagnosis of PCNA need systemic evaluation and long-term followup. ● Psoriasis is associated with an increased risk of plasma cell dyscrasias, and this report suggests a possible association with PCNA. ● Hyaline eosinophilic deposits in colloid milium, lipoid proteinosis, the porphyrias and Waldenstrom macroglobulinaemia can mimic amyloid histologically.
References 1 Fernandez-Flores A. Cutaneous amyloidosis: a concept review. Am J Dermatopathol 2012; 34: 1–14; quiz 15–17.
ª 2014 British Association of Dermatologists
2 Schreml S, Szeimies RM, Vogt T et al. Cutaneous amyloidosis and systemic amyloidoses with cutaneous involvement. Eur J Dermatol 2010; 20: 152– 60. 3 Woollons A, Black MM. Nodular localized primary cutaneous amyloidosis: a long-term follow-up study. Br J Dermatol 2001; 145: 105–9. 4 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. 5 Lee DY, Kim YJ, Lee JY et al. Primary localized cutaneous nodular amyloidosis following local trauma. Ann Dermatol 2011; 23: 515–18. 6 Elloso MM, Gomez-Angelats M, Fourie AM. Targeting the Th17 pathway in psoriasis. J Leukoc Biol 2012; 92: 1187–97. 7 Prabhala RH, Pelluru D, Fulciniti M et al. Elevated IL-17 produced by Th17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010; 115: 5385–92. 8 Noonan K, Marchionni L, Anderson J et al. A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 2010; 116: 3554–63. 9 Wittenberg GP, Oursler JR, Peters MS. Secondary amyloidosis complicating psoriasis. J Am Acad Dermatol 1995; 32: 465–8. 10 Eder L, Thavaneswaran A, Pereira D et al. Prevalence of monoclonal gammopathy among patients with psoriatic arthritis. J Rheumatol 2012; 39: 564–7.
Clinical and Experimental Dermatology (2014) 39, pp608–611
611
