Macular amyloidosis diagnostic outcomes of skin biopsy: A systematic review.

Macular amyloidosis (MA) is a primary localized cutaneous amyloidosis, characterized by amyloid deposition in the papillary dermis. The clinical presentation includes pruritic hyperpigmented macules and patches with a reticulated or rippled pattern, primarily found on the upper back and extremities. Biopsy is an essential diagnostic tool for confirming MA. This systematic review focused on the biopsy outcomes in patients diagnosed with MA.

Evaluation of Psychopathologies and Health-Related Quality of Life in Patients With Macular Amyloidosis / Evaluación de psicopatologías y calidad de vida relacionada con la salud en pacientes con amiloidosis macular

Macular amyloidosis (MA) is a skin condition with predominance in young women. We aimed to evaluate quality of life (QoL) and psychopathologies in these patients. In this cross-sectional study, patients with MA referring to the Imam Reza Hospital, Mashhad during 2018–2020, and their matched controls were included. Participants completed the 36-item short form survey (SF-36), the revised symptom checklist-90 (SCL-90-R), and the dermatology life quality index (DLQI). Overall, 40 women with a mean age of 36.80±10.19 years were studied. In the MA group, the SF-36 score was lower (P<0.001), and the SCL-90-R score was higher (P<0.001). The DLQI score was correlated with age (r=0.447; P=0.048) and pruritus severity (r=0.776; P<0.001), and was lower in patients with uncovered lesions (P=0.005). MA was associated with impaired QoL, which was determined by pruritus severity and lesion location; these patients can benefit from psychiatric interventions in this regard (AU)

La amiloidosis macular (AM) es una situación cutánea con predominancia en mujeres jóvenes. Nuestro objetivo fue evaluar la calidad de vida (QoL) y las psicopatologías en estos pacientes. En este estudio transversal se incluyó a pacientes con AM derivados al Hospital Imam Reza, de Mashhad, de 2018 a 2020, así como a sus controles pareados. Los participantes completaron la encuesta SF-36 (formulario breve de 36 ítems), el test de los 90 síntomas revisado (SCL-90-R) y el índice de calidad de vida en dermatología (DLQI). A nivel global, se estudió a 40 mujeres con una edad media de 36,80±10,19 años. En el grupo AM, la puntuación SF-36 fue más baja (p<0,001), siendo más alta la puntuación SCL-90-R (p<0,001). La puntuación DLQI se correlacionó con la edad (r=0,447; p=0,048) y con la severidad del prurito (r=0,776; p<0,001), siendo más baja en las pacientes con lesiones sin cubrir (p=0,005). La AM estuvo asociada a un deterioro de la QoL, que vino determinada por la severidad del prurito y la localización de la lesión. A este respecto, dichas pacientes pueden beneficiarse de intervenciones psiquiátricas (AU)

[Artículo traducido] Evaluación de psicopatologías y calidad de vida relacionada con la salud en pacientes con amiloidosis macular / Evaluation of Psychopathologies and Health-Related Quality of Life in Patients With Macular Amyloidosis

La amiloidosis macular (AM) es una situación cutánea con predominancia en mujeres jóvenes. Nuestro objetivo fue evaluar la calidad de vida (QoL) y las psicopatologías en estos pacientes. En este estudio transversal se incluyó a pacientes con AM derivados al Hospital Imam Reza, de Mashhad, de 2018 a 2020, así como a sus controles pareados. Los participantes completaron la encuesta SF-36 (formulario breve de 36 ítems), el test de los 90 síntomas revisado (SCL-90-R) y el índice de calidad de vida en dermatología (DLQI). A nivel global, se estudió a 40 mujeres con una edad media de 36,80±10,19 años. En el grupo AM, la puntuación SF-36 fue más baja (p<0,001), siendo más alta la puntuación SCL-90-R (p<0,001). La puntuación DLQI se correlacionó con la edad (r=0,447; p=0,048) y con la severidad del prurito (r=0,776; p<0,001), siendo más baja en las pacientes con lesiones sin cubrir (p=0,005). La AM estuvo asociada a un deterioro de la QoL, que vino determinada por la severidad del prurito y la localización de la lesión. A este respecto, dichas pacientes pueden beneficiarse de intervenciones psiquiátricas (AU)

Macular amyloidosis (MA) is a skin condition with predominance in young women. We aimed to evaluate quality of life (QoL) and psychopathologies in these patients. In this cross-sectional study, patients with MA referring to the Imam Reza Hospital, Mashhad during 2018–2020, and their matched controls were included. Participants completed the 36-item short form survey (SF-36), the revised symptom checklist-90 (SCL-90-R), and the dermatology life quality index (DLQI). Overall, 40 women with a mean age of 36.80±10.19 years were studied. In the MA group, the SF-36 score was lower (P<0.001), and the SCL-90-R score was higher (P<0.001). The DLQI score was correlated with age (r=0.447; P=0.048) and pruritus severity (r=0.776; P<0.001), and was lower in patients with uncovered lesions (P=0.005). MA was associated with impaired QoL, which was determined by pruritus severity and lesion location; these patients can benefit from psychiatric interventions in this regard (AU)

Evaluation of Psychopathologies and Health-Related Quality of Life in Patients With Macular Amyloidosis. / [Artículo traducido] Evaluación de psicopatologías y calidad de vida relacionada con la salud en pacientes con amiloidosis macular.

Macular amyloidosis (MA) is a skin condition with predominance in young women. We aimed to evaluate quality of life (QoL) and psychopathologies in these patients. In this cross-sectional study, patients with MA referring to the Imam Reza Hospital, Mashhad during 2018-2020, and their matched controls were included. Participants completed the 36-item short form survey (SF-36), the revised symptom checklist-90 (SCL-90-R), and the dermatology life quality index (DLQI). Overall, 40 women with a mean age of 36.80±10.19 years were studied. In the MA group, the SF-36 score was lower (P<0.001), and the SCL-90-R score was higher (P<0.001). The DLQI score was correlated with age (r=0.447; P=0.048) and pruritus severity (r=0.776; P<0.001), and was lower in patients with uncovered lesions (P=0.005). MA was associated with impaired QoL, which was determined by pruritus severity and lesion location; these patients can benefit from psychiatric interventions in this regard.

Evaluation of Psychopathologies and Health-Related Quality of Life in Patients With Macular Amyloidosis.

Macular amyloidosis (MA) is a skin condition with predominance in young women. We aimed to evaluate quality of life (QoL) and psychopathologies in these patients. In this cross-sectional study, patients with MA referring to the Imam Reza Hospital, Mashhad during 2018-2020, and their matched controls were included. Participants completed the 36-item short form survey (SF-36), the revised symptom checklist-90 (SCL-90-R), and the dermatology life quality index (DLQI). Overall, 40 women with a mean age of 36.80±10.19 years were studied. In the MA group, the SF-36 score was lower (P<0.001), and the SCL-90-R score was higher (P<0.001). The DLQI score was correlated with age (r=0.447; P=0.048) and pruritus severity (r=0.776; P<0.001), and was lower in patients with uncovered lesions (P=0.005). MA was associated with impaired QoL, which was determined by pruritus severity and lesion location; these patients can benefit from psychiatric interventions in this regard.

AHNAK, regulated by the OSM/OSMR signaling, involved in the development of primary localized cutaneous amyloidosis.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disease characterized by aberrant keratinocyte differentiation, epidermal hyperproliferation, and amyloid deposits. Previously, we demonstrated OSMR loss-function mutants enhanced basal keratinocyte differentiation through the OSMR/STAT5/KLF7 signaling in PLCA patients. OBJECTIVE: To investigate the underlying mechanisms involved in basal keratinocyte proliferation in PLCA patients that remain unclear. METHODS: Patients with pathologically confirmed PLCA visiting the dermatologic outpatient clinic were involved in the study. Laser capture microdissection and mass spectrometry analysis, gene-edited mice, 3D human epidermis culture, flow cytometry, western blot, qRT-PCR and RNA sequencing were used to explore the underlying molecular mechanisms. RESULTS: In this study, we found that AHNAK peptide fragments were enriched in the lesions of PLCA patients, as detected by laser capture microdissection and mass spectrometry analysis. The upregulated expression of AHNAK was further confirmed using immunohistochemical staining. qRT-PCR and flow cytometry revealed that pre-treatment with OSM can inhibit AHNAK expression in HaCaT cells, NHEKs, and 3D human skin models, but OSMR knockout or OSMR mutations abolished this down-regulation trend. Similar results were obtained in wild-type and OSMR knockout mice. More importantly, EdU incorporation and FACS assays demonstrated the knockdown of AHNAK could induce G1 phase cell cycle arrest and inhibit keratinocyte proliferation. Furthermore, RNA sequencing revealed that AHNAK knockdown regulated keratinocyte differentiation. CONCLUSION: Taken together, these data indicated that the elevated expression of AHNAK by OSMR mutations led to hyperproliferation and overdifferentiation of keratinocytes, and the discovered mechanism might provide insights into potential therapeutic targets for PLCA.

Immunoglobulin G4-Related Disease-Associated Dermatitis with Pruritus: A Positive Response to Dupilumab.

Immunoglobulin G4-related disease (IgG4-RD) is a rare fibro-inflammatory condition characterized by IgG4-expressing plasma cell infiltration of the skin and other organs, leading to profound itchiness. Oral corticosteroids are the first-line therapy for IgG4-RD but relapses and potential side effects are common. In this case, we discuss a patient with a hyperpigmented, scaling dermatitis on his arms, back, and chest with lichen amyloidosis (LA) that incompletely responded to corticosteroids. He had reduced quality of life secondary to chronic pruritus. Dupilumab, an IL-4 and IL-13 inhibitor, was initiated. He experienced a transient worsening, followed by complete resolution of his itch with remission of his rash. While the pathogenesis of IgG4-RD is not entirely understood, a T-helper 2 (Th2) immune response has been implicated, with interleukins (IL) 4, 5, 10, and 13 playing a role in IgG4 class switch, resulting in eosinophilia and elevated IgE. The strong response of dupilumab in this case may provide evidence in favor of the involvement of IL-4 and IL-13 in the pathogenesis of cutaneous IgG4-RD. Future clinical studies involving larger patient populations may be warranted.

Fibulin-4 Accelerates Amyloid Formation by Binding with a Keratin 5 Peptide Fragment.

Keratins are the major amyloid fibril component in localized cutaneous amyloidosis. We analyzed the amyloid components in the skin of patients with localized cutaneous amyloidosis by immunohistochemical staining using antisera against extracellular matrix proteins and keratin 5 (K5). Fibulin-4 and K5 colocalized in the amyloid deposits. Using 14 synthetic peptides, we screened for amyloidogenic sequences in the C-terminal region of K5, including the α-helical rod domain and the tail domain. Two peptides stained with thioflavin T possessed a ß-sheet structure and formed amyloid-like fibrils. Among the amyloidogenic peptides, a peptide KT5-6 (YQELMNTKLALDVEIATYRKLLEGE) derived from the α-helical rod domain of K5 specifically bound to fibulin-4. In addition, amyloid formation of KT5-6 was accelerated by fibulin-4. These results suggest that degraded fragments of K5 containing the KT5-6 sequence form amyloid fibrils with fibulin-4. The data further suggest that degraded fragments of K5 and fibulin-4 have the potential to initiate cutaneous amyloidosis.

Primary Localized Cutaneous Amyloidosis: A Retrospective Study of an Uncommon Skin Disease in the Largest Tertiary Care Center in Switzerland.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is defined by the deposition of amyloid protein in the skin without systemic involvement. There are four subtypes of PLCA: lichen amyloidosis (LA), macular amyloidosis (MA), biphasic amyloidosis (BA), and nodular amyloidosis (NA). PLCA occurs most frequently in Latin Americans and Asians. Treatment is not standardized. OBJECTIVES: To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA. MATERIALS AND METHODS: Data of PLCA patients were extracted from the electronic hospital database and included if diagnosis of PLCA was histopathologically confirmed and if sufficient information regarding treatment and follow-up was available. The evaluation of the treatment efficacy was based on a novel score to assess the reduction of itch and skin lesions. RESULTS: In this retrospective, monocentric study, 37 cases of PLCA diagnosed between 2000 and 2020 were included (21 females) with a mean age of 52 years. LA was the most frequent subtype found in 21 patients (56.8%), followed by MA in 10 patients (28%) and BA in 6 patients (16.2%). No cases of NA were included. 22 patients (59.4%) had skin phototype II or III. Regarding treatment, a combination of UVA1 phototherapy with high-potency topical corticosteroids seemed to show the highest efficacy with complete clearance of symptoms in 4 patients (10.8%). A substantial improvement of symptoms was found in 5 patients (12.7%) treated with high-potency topical corticosteroids alone or in combination either with UVA1 or bath PUVA or monotherapy with UVA1 phototherapy or capsaicin (0.075%) cream. Low-/medium-potency topical corticosteroids alone or in combination with UVBnb (311 nm) phototherapy showed a lower efficacy. CONCLUSION: Our data show that PCLA is a rare disease in central Europe but can also be expected in a predominantly Caucasian population. The best treatment response was achieved with a combination of UVA1 phototherapy and high-potency topical corticosteroids.

Efficacy of 1064-nm Nd:YAG picosecond laser in lichen amyloidosis treatment: clinical and dermoscopic evaluation.

Lichen amyloidosis (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple localized, hyperpigmented, grouped papules, in which the deposition of amyloid materials from altered keratinocytes usually resists to current treatments. We presented two LA patients with non-satisfactory results of topical treatments. After the first treatment using 1064-nm Nd: YAG picosecond (ps-Nd:YAG) laser, there was an improvement with persistence up to 3-month follow up after five sessions of 4-week interval, as well as a decrease in number, thickness, and darkness of lesions from clinical and dermoscopic evaluation. Thus, the ps-Nd:YAG laser could be efficacious for LA treatment.

A Rare Presentation of Nodular Amyloidosis on the Lower Back.

Primary localized cutaneous amyloidosis (PLCA) occurs when amyloid is deposited only within the skin and there is no evidence of systemic involvement. Nodular amyloidosis is the rarest subtype of PLCA. It typically involves the acral regions but can sometimes present on the head and neck. The condition usually presents clinically as a single tan or yellow nodule or plaque that may appear waxy. Herein, we present a rare case of a 66-year-old man with nodular amyloidosis on the lower back.

Nodular cutaneous amyloidoma of the extremity secondary to chronic granulomatous inflammation in setting of sarcoidosis.

Soft tissue amyloidoma is a rare condition that presents primarily in the abdomen and/or mediastinum and more uncommonly on the extremities. Soft tissue amyloidomas on the extremities have been associated with chronic inflammation, particularly when accompanied by AA-type amyloid deposition as seen in local trauma, surgery, hypertension and diabetes. To our knowledge, this is the first reported case of nodular cutaneous amyloidoma in the setting of systemic and cutaneous sarcoidosis. A 65-year-old woman presented with an asymptomatic subcutaneous nodule above her left lateral malleolus. Histopathology of the lesion showed an inconspicuous epidermis with amorphous eosinophilic material deposited in masses within the entire dermis. Congo red and crystal violet stains were positive. Based on the clinical and pathologic findings she was diagnosed with nodular cutaneous amyloidoma. We hypothesize that this process developed secondary to the chronic granulomatous inflammation of sarcoidosis.

Nodular Cutaneous Amyloidosis Resembling a Giant Tumor.

A 79-year-old man presented with a large tumor on the left side of his head, which had grown over 5 years. Regional lymph nodes were impalpable and computed tomography revealed no signs of bone infiltration. Histology showed that the entire dermis was filled with amorphous eosinophilic material. Immunohistochemistry was negative for cytokeratin, but showed that the dermis and parts of the subcutis were filled with amyloid consisting of immunoglobulin light chains. There were no signs of paraproteinemia or underlying plasmocytoma. In electron microscopy, the typical amyloid fibrils were found. The tumor was completely removed via curettage. At 1-year follow-up, the patient was doing fine with no signs of relapse or systemic disease.

[Primary localized cutaneous nodular amyloidosis: A diagnostic and therapeutic challenge]. / Amylose cutanée nodulaire primitive localisée: un défi diagnostique et thérapeutique.

BACKGROUND: Nodular primary localized cutaneous amyloidosis (PLCA) is a rare subtype of localized cutaneous amyloidosis in which amyloid protein is derived from immunoglobulin light chains. Follow-up for progression to systemic amyloidosis or autoimmune disease is mandatory. No consensus exists regarding treatment. PATIENTS AND METHODS: We report a case of nodular PLCA in a 49-year-old man, presenting as an asymptomatic nodule of the nose. Skin biopsy revealed diffuse deposition of amyloid associated with plasmocyte proliferation. Monotypic kappa light-chain restriction was observed. Extensive systemic evaluation, including bone marrow biopsy and PET scan, was negative. Protein electrophoresis and immunofixation in serum and urine were normal. The nodule was treated with radiotherapy but there was no response. Mohs micrographic surgery (MMS) was performed with no recurrence at 6 months of follow-up. No systemic progression was observed one year after the initial diagnosis. DISCUSSION: Since nodular PLCA may have a cutaneous presentation similar to that of primary systemic amyloidosis, evaluation for systemic amyloidosis is necessary. Treatment of amyloidosis is difficult. Radiotherapy appears ineffective in treating this type of primary cutaneous amyloidosis, and surgical treatment, where possible, is a good option, especially with MMS, which allows both controlled excision and minimal margins.

Itch in familial lichen amyloidosis: effective treatment with amitriptyline in two cases.

Itch is a characteristic feature of lichen amyloidosis and the symptom can be debilitating. Treatments, however, are generally not effective. We report amitriptyline as a novel therapy in treating itch in two patients with familial lichen amyloidosis who did not respond to prior potent topical corticosteroids and antihistamines. Outcomes of treatment were assessed using the itch score on a visual analog scale, itch frequency, and the Dermatology Life Quality Index (DLQI). After taking amitriptyline 10 mg o.n. for 6 weeks, the itch score of one patient was reduced from 8.5 to 2 of 10, whereas the second patient's itch score was reduced from 5 to 1. In the latter, his DLQI concurrently reduced from 14 to 6 of 30. Pathophysiology of itch in lichen amyloidosis may involve both cutaneous and neural components and amitriptyline is known to be useful for neuropathic itch. Low-dose amitriptyline poses little risk of side effects and may offer an effective and safe alternative for the treatment of itch in familial cutaneous amyloidosis.

Lichen amyloidosis in a 57 year old female: A case report

We describe a case of a 57 year old female who presented with multiple papules on bilateral extremities with no other systemic findings. Skin lesions consisted of multiple hyperpigmented scaly papules in a rippled pattern some coalescing into plaques. Histologic examination showed deposits of amorphous eosinophilic materials in the papillary dermis. The diagnosis of lichen amyloidosis was made. Treatment with high potency topical steroid in combination with salicylic acid ointment, emollients, and systemic antihistamine which afforded improvement after 2 weeks. There was 90 percent clearance of lesion within 5 months of therapy. The origin and clinical features of papular primary localized cutaneous amyloidosis (PLCA) are reviewed.

A Case of Familial Primary Localized Cutaneous Amyloidosis / 대한피부과학회지

Primary localized cutaneous amyloidosis comprises macular, papular and rare nodular amyloidosis. Macular and papular amyloidosis are considered as different manifestations of the same disease process and can occur in the same patient, which is known as biphasic amyloidosis. Although most cases of primary cutaneous amyloidosis occur sporadically, some cases have been reported to have familial incidence with papular, biphasic or rarely macular amyloidosis. We report a case of a family in which a mother and her son have brown hyperkeratotic pruritic papules on both upper and lower extremities. The skin lesions initially began as macules on the shins in the second or third decade, but gradually spread with increasing papules and pigmentation. They had no kind of manifestation suggesting systemic amyloidosis. A skin biopsy specimen disclosed amyloid deposition in papillary dermis.

A Case of Familial Primary Localized Cutaneous Amyloidosis / 대한피부과학회지

Primary localized cutaneous amyloidosis comprises macular, papular and rare nodular amyloidosis. Macular and papular amyloidosis are considered as different manifestations of the same disease process and can occur in the same patient, which is known as biphasic amyloidosis. Although most cases of primary cutaneous amyloidosis occur sporadically, some cases have been reported to have familial incidence with papular, biphasic or rarely macular amyloidosis. We report a case of a family in which a mother and her son have brown hyperkeratotic pruritic papules on both upper and lower extremities. The skin lesions initially began as macules on the shins in the second or third decade, but gradually spread with increasing papules and pigmentation. They had no kind of manifestation suggesting systemic amyloidosis. A skin biopsy specimen disclosed amyloid deposition in papillary dermis.