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.

Breast amyloidosis associated with Sjögren syndrome: A diagnostic pitfall in breast pathology.

BACKGROUND: Amyloidosis is an uncommon disorder characterized by the extracellular deposition of amorphous and insoluble proteins in an abnormal fibrillary configuration. Mammary amyloidosis is an unusual and easily overlooked diagnosis with an ambivalent presentation that could mimic breast cancer. CASE REPORT: We here report the case of 60-year-old Caucasian woman who presented to our surgical oncology department for clinically and radiologically suspicious breast mass. A fine needle biopsy was irrelevant, so we performed a lumpectomy. Final histology revealed an amyloid deposit and further workup was consistent with nodular cutaneous and breast AL amyloidosis associated with Sjögren's syndrome. CONCLUSION: Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for breast surgeons.

Characterization of Epidermal Function in Individuals with Primary Cutaneous Amyloidosis.

Purpose: To compare epidermal biophysical properties, indicators of epidermal function, in individuals with and without primary cutaneous amyloidosis (PCA). Patients and Methods: This study incorporated 189 patients with PCA and 166 healthy individuals. The GPSkin Barrier was employed to measure transepidermal water loss (TEWL) rates and hydration levels of the stratum corneum. The Sebumeter and the Skin pH Meter were utilized to determine the skin surface's sebum content and pH, respectively. The severity of pruritus in participants was evaluated using the visual analog scale (VAS). Results: Compared to the control group without PCA, individuals with PCA displayed a notable increase in skin surface pH and TEWL and a decrease in the hydration levels of the stratum corneum (p<0.0001 for all parameters). Additionally, the sebum content was markedly lower in those with PCA than in the controls (p<0.0001). Of particular note, both TEWL and skin surface pH at the lesion sites on the back and the shin were more elevated in lichenoid amyloidosis (LA) and in macular amyloidosis (MA), whereas hydration levels of the stratum corneum and sebum levels were diminished in LA compared to MA (p<0.05). In conclusion, both hydration levels of the stratum corneum and sebum content exhibited an inverse relationship with pruritus severity, whereas TEWL and skin surface pH demonstrated a positive correlation with pruritus intensity. Conclusion: The function of the epidermis is compromised in individuals diagnosed with PCA. However, the mechanisms underlying these changes await further investigation.

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.

Barrier function and ultrastructure characteristics of epidermis in patients with primary cutaneous amyloidosis.

Previous studies on primary cutaneous amyloidosis (PCA) have mainly focused on exploring genetic mutation and components of amyloid in patients with PCA. However, studies on skin barrier function in PCA patients are scarce. Here, we detected the skin barrier function in PCA patients and healthy people by using noninvasive techniques and characterized ultrastructural features of PCA lesions compared with healthy people using transmission electron microscopy (TEM). The expression of proteins related to skin barrier function was examined by immunohistochemistry staining. A total of 191 patients with clinically diagnosed PCA and 168 healthy individuals were enrolled in the study. Our analysis revealed that all investigated lesion areas displayed higher transepidermal water loss and pH values, and lower Sebum levels and stratum corneum hydration levels in PCA patients compared with the same site area in healthy individuals. The TEM results showed that the intercellular spaces between the basal cells were enlarged and the number of hemidesmosomes decreased in PCA lesions. Immunohistochemical staining showed that the expression of integrin α6 and E-cadherin in PCA patients was less than that in healthy controls, while no differences in the expression of loricrin and filaggrin were observed. Our study revealed that individuals with PCA displayed skin barrier dysfunction, which may be related to alterations in epidermal ultrastructure and a decrease in the skin barrier-related protein E-cadherin. However, the molecular mechanisms underlying skin barrier dysfunction in PCA remain to be elucidated.

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.

Case report: Complex paraneoplastic syndromes in thymoma with nephrotic syndrome, cutaneous amyloidosis, myasthenia gravis, and Morvan's syndrome.

Background: Apart from myasthenia gravis (MG), thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes (PNSs). Here, we report on a rare case presenting with four different PNSs, namely, MG, membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome associated with thymoma. Case presentation: A middle-aged man was frequently hospitalized because of nephrotic syndrome (stage I membranous nephropathy), cutaneous amyloidosis, and MG with acetylcholine receptor (AChR) antibody and titin antibody positivity. Chest CT showed a thymic mass in the left anterior mediastinum, and he received intravenous immunoglobulin (IVIG), methylprednisolone pulse therapy, thoracoscopic thymoma resection, and radiotherapy. Postoperative pathological examination revealed a type B2 thymoma. During the perioperative stage, his electrocardiogram (ECG) showed myocardial infarction-like ECG changes; however, his levels of cardiac enzymes and troponin were normal, and he had no symptoms of precardiac discomfort. Six months after thymectomy, his nephrotic syndrome and MG symptoms were relieved; however, he presented with typical manifestations of Morvan's syndrome, including neuromyotonia, severe insomnia, abnormal ECG activity, and antibodies against leucine-rich glioma-inactivated 1 (LGI1) and γ-amino-butyric acid-B receptor (GABABR). His symptoms did not improve after repeated IVIG and steroid therapies. Finally, he received low-dose rituximab, and his symptoms gradually resolved. Conclusion: This case serves to remind us that apart from MG, thymoma is also associated with other autoimmune PNSs such as membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome. Autoimmune PNSs can present concurrently with or after surgical or medical therapy for thymoma. For Morvan's syndrome post-thymectomy with LGI1 antibody positivity, B-cell depletion therapy such as intravenous rituximab is an effective treatment.

Topical halometasone cream combined with fire needle pre-treatment for treatment of primary cutaneous amyloidosis: Two case reports.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a chronic metabolic skin disease that has a detrimental impact on physical and mental health. It appears as mossy papules and severe itching, which is long-term and recurrent. Traditional treatments are unsatisfactory, especially for refractory cases. Fire needle therapy, which is widely used in China, has shown good clinical efficacy, as well as advantages concerning safety and cost. Clinical reports about fire needle treatment of this disease are few at present. CASE SUMMARY: We report two older men who had developed maculopapules with itchiness on the trunk and arms for more than 10-15 years. Due to the dermatopathological findings, PCA was our primary consideration. They received topical halometasone cream and pretreatment with fire needle for 8-16 wk. Both patients showed significant improvement of lesions. Neither patient had recurrence with a minimum of 2 years of follow-up. CONCLUSION: Topical halometasone cream and pretreatment with fire needle could be a fast, safe, and economic treatment for PCA.

A Case of Perifollicular Macular Amyloidosis.

Macular amyloidosis is a common type of primary localized cutaneous amyloidosis. We present a case report of a 74-year-old patient with no significant past medical history who was evaluated for dark macules and pruritus for over a year. On exam, follicular-based brown macules on the upper and lower back, bilateral shoulders, and bilateral dorsal upper arms were noted. The morphology and distribution of follicular-based macules was unusual, so the differential included follicular lichen planus, follicular eczema, and macular amyloidosis. Punch biopsy showed deposits of eosinophilic fibrillary material along with pigmentary incontinence in the papillary dermis, consistent with macular amyloidosis. Additionally, there was some trapping of the adnexal structures with atrophy of the periadnexal fat in the reticular dermis. In macular amyloidosis keratin, intermediate filaments such as cytokeratin serve as the amyloid precursors which deposit in the superficial dermis. Characteristically, macular amyloidosis presents as hyperpigmented macules or patches, often in a "rippled" linear pattern. This case highlights a rare presentation of macular amyloidosis because of the atypical follicular involvement and emphasizes the variety of presentations for localized cutaneous amyloidosis. Additionally, new treatment options such as Janus Kinase inhibitors and their potential role in the pathological pathway are discussed.

Dermoscopy aids in differentiating primary cutaneous amyloidosis and post-inflammatory hyperpigmentation: A clinico-dermoscopic-histopathaological study.

BACKGROUND: Primary cutaneous amyloidosis (PCA) and post-inflammatory hyperpigmentation (PIH) are common causes of cutaneous hyperpigmentation that are usually diagnosed clinically. However, their presentations are sometimes atypical, and their differentiation is difficult. Dermoscopy is a valuable diagnostic tool for pigmented diseases that might aid in their diagnosis. OBJECTIVE: To describe the characteristic dermoscopic features of PCA and PIH together with histopathological correlation, and to differentiate between these conditions in a non-invasive way. METHODS: Fifty-two patients with PCA (n = 26) and PIH (n = 26) were enrolled. A detailed history, skin examination, dermoscopic examination using handheld and video dermoscopy, and histopathological evaluation were performed. RESULTS: A statistically significant difference could be detected between PCA and PIH in terms of the duration of the disease (p = 0.027), symmetry (p = 0.044), rippling (p < 0.001), and back affection (p = 0.048). On dermoscopic examination, central hubs were seen more in the PCA group (p < 0.001) with different patterns of peripheral pigmentation. Histopathologically, the number of melanophages per high-power field was significantly higher in the PCA group (p = 0.013). CONCLUSION: The results of this study shed the light on the potential of dermoscopy as a non-invasive diagnostic tool in differentiating between doubtful cases of PCA and PIH.

Lichen Amyloidosis on the Scalp: A Case Report.

Lichen amyloidosis (LA) is one form of primary cutaneous amyloidosis, presented as discrete, lichenoid papules with itching, commonly involving the extensor surfaces of extremities. Scalp involvement is rarely reported in the literature. In this study, we reported a case of LA over the crown and vertex areas of the scalp. The lesions subsided with topical clobetasol propionate/all-trans retinoic acid compound ointment treatment for 2 months and achieved significant improvement.

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.

Multiple Indolent Asymptomatic Yellow-Orange Patches and Plaques.

An 83-year-old Caucasian male presented with a history of asymptomatic yellow-orange macules and plaques concentrated on his trunk and proximal extremities that have been slowly progressing for the past three years. A punch biopsy revealed the presence of eosinophilic amorphous and fissured material within the superficial and interstitial dermis consistent with nodular amyloidosis. With the lack of concurrent systemic symptoms and negative systemic laboratory workup, the patient was diagnosed with disseminated primary localized cutaneous nodular amyloidosis (PLCNA). Due to the possibility of developing systemic progression, serial monitoring was recommended. This case highlights an under-reported and unusual presentation of a widely distributed form of PLCNA compared to the more common localized nodular and plaque variants.