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

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA. <b><i>Materials and Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Morphea: LED Technologie sorgt für verbesserte Phototherapie

Ultraviolet A₁ (UVA₁) phototherapy (spectral range 340–400nm) is a well-established treatment option for various skin diseases such as localized scleroderma. Recent improvements of conventional UVA₁ light sources (metal-halide or fluorescent lamps) have brought attention to a new light-emitting diode (LED) technology with remarkable advantages in handling and clinical routine. This study provides a preclinical histological and molecular evaluation of an LED-based UVA1 prototype with a narrower spectral range (360–400nm) for treating localized scleroderma. Scleroderma mouse models and fibroblasts in vitro were exposed to LED-based UVA₁ phototherapy or to irradiation with a commercially available metal-halide lamp emitting low-dose (20, 40J/cm²), medium-dose (60J/cm²) and high-dose (80, 100J/cm²) UVA₁ light. Both UVA₁ light sources affected inflammatory genes (IL-1α and IL-6) and growth factors (TGFß-1 and TGFß-2). Increased collagen type 1 was reduced after UVA₁ phototherapy. Matrix metalloproteinase-1 was more enhanced after a medium dose of LED-based UVA1 phototherapy than after conventional treatment. In vivo, dermal thickness and the amount of collagen were reduced after both treatment methods. Remarkably, myofibroblasts were more effectively reduced by a medium dose of LED-based UVA1 phototherapy. The study indicates that LED-based UVA₁ phototherapy yields similar or even better results than conventional treatment. In terms of biosafety and patient comfort, LED-based UVA₁ phototherapy offers clear advantages over conventional treatment because of the use of a narrower and less harmful UVA₁ spectrum, less heat generation and shorter treatment times at the same irradiation intensity. Clinical studies are required to confirm these results in patients with localized scleroderma.

Effect of UVA1 on hypertrophic scarring in the rabbit ear model

Hypertrophic scars (HTSs) are common and cause functional and psychological morbidity. UVA1 (340–400 nm) phototherapy has been previously shown to be effective in the treatment of localized scleroderma, systemic sclerosis, and POEMS syndrome with minimal side effects, all of which are presented as collagen fibrils hyperplasia that is common with scarring in skin histology. In the present study, we aimed to investigate the impact of UVA1 on the protein expression of TGF-β signal pathway and myofibroblasts in a rabbit model of cutaneous scarring. Full-thickness skin wounds (2 cm × 5 cm in diameter) were made in New Zealand white rabbits to establish the hypertrophic scarring model. New Zealand white rabbits were divided into two treatment groups (n=30 wounds per group with an equal number of controls): medium-dose of UVA1 phototherapy group: 60 J/cm2; high-dose of UVA1 phototherapy group: 110 J/cm2. Left ears were used for treatment and the right ones were used for control. Treatment was administered five times weekly for 6 weeks. Treated and untreated control wounds were harvested at various time points and examined by histologic examination, immunohistochemical assessment, and ultrastructural evaluation. The results showed that UVA1 phototherapy caused a significant reduction in dermal thickness by histological features, whereas the scar index was descended significantly in both medium- and high-dose UVA1 groups compared with the control group. Examination of immunohistochemistry also revealed a marked suppression of tissue growth factor-β (TGF-β) (both medium- and high-dose), α smooth muscle actin (α-SMA) (only high-dose), and tissue inhibitor of metalloproteinase 1 (TIMP-1) (only high-dose), and apparent increase in matrix metalloproteinases (MMP-1) (both medium- and high-dose) compared with the control. The ultrastructural evaluation showed the collagen fibers’ diameter had shrunk, and that fibroblastic cytoplasm was not affluent and in a quiescent stage. These findings of the present study suggested that administration of UVA1 irradiation is effective to improve the experimental HTS model and raises a possibility of the therapeutic approach of UVA1 in the scar. Although not directly examined in the present study, MMP inhibition is hypothesized to be responsible for this effect. However, early UVA1 treatment could not prevent the formation of scar model.