¹Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
²Baywood Dermatology and CCA Medical Research, Ajax, ON, Canada
³Probity Medical Research, Waterloo, ON, Canada
⁴Dermatology on Bloor, Toronto ON, Canada
⁵Skin Centre for Dermatology, Peterborough, ON, Canada
⁶imc North America, Toronto, ON, Canada
⁷LEO Pharma Inc. Canada, Thornhill, ON, Canada

Conflict of interest:
D. Adam has been an investigator, speaker, or advisory board member for LEO Pharma, AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, BMS, Celgene, Coherus, Dermira, Dermavant, Eli Lilly, Galderma, Incyte, Janssen, Merck, Novatrtis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB. S. Abdulla has been a speaker or advisory board member for LEO Pharma, AbbVie, Celgene, Eli Lilly, Galderma, Janssen, Novartis, Pfizer, Sanofi Genzyme, UCB, and Bausch/Valeant. P. Fleming has received honorarium and/or consulting and/or advisory boards and/or speaking fees for AbbVie, Altius, Aralez, Bausch Health, Cipher, Galderma, Eli Lilly, UCB, Janssen, Novartis, Pfizer, and Sanofi-Genzyme. M. Gooderham has been an investigator, speaker, or advisory board member for LEO Pharma, AbbVie, Amgen, Akros, Arcutis, Boehringer Ingelheim, BMS, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Janssen, Kyowa Kirin, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Bausch/Valeant. J. Ashkenas received support via imc North America (Toronto, ON) from LEO Pharma Inc. Canada for participating in the development of the practice reflective and for analyzing the findings. He has no other financial interest to declare. C. McCracken is employed by LEO Pharma Inc. Canada.

Abstract:
Patient preferences for psoriasis treatment may affect treatment adherence and disease control; changing topical formulation may improve adherence and patient acceptance of treatment. This study explored dermatologists’ reasons for transitioning psoriasis patients from an ointment or gel (Dovobet^®) formulation to an aerosol foam (Enstilar^®) formulation of calcipotriol and betamethasone dipropionate (Cal/BD), and to assess the success of this transition. Medical records of 81 Canadian patients from 9 dermatologists were retrospectively reviewed for symptoms affecting quality of life, reasons for transitioning treatment, and whether transition was successful. Reasons for transition included efficacy, quality of life, and patient adherence. At follow-up, median psoriasis severity and body surface area affected had decreased from baseline, and patients experienced improved quality of life. Itch and itch-related sleep loss, which were identified as burdensome in 63% of patients at baseline, had resolved in 33% and improved in 54% of patients at follow-up. Dermatologists deemed the transition successful in 85% of patients, with the most common reasons being patient-reported success, clearance of signs/symptoms, and continued prescription refills. Transition from Cal/BD ointment or gel to aerosol foam was generally deemed successful by patients and dermatologists, and was associated with improved quality of life and improved itch control.

Key Words:
psoriasis; topical treatment; foam; formulation; fixed combination

Introduction

Psoriasis is a chronic condition that commonly requires topical treatment, either as monotherapy or in combination with phototherapy or systemic treatment. Given the challenge of consistent long-term adherence to treatment for psoriasis,^1-3 patient acceptance of topical treatment is an important consideration.^4,5 Formulations with more appealing cosmetic features could affect patient acceptance, and therefore adherence and ultimately disease control.^6-9

Calcipotriol and betamethasone dipropionate (Cal/BD) are the active ingredients in Dovobet^® ointment or gel (Cal/BD ointment or gel) and Enstilar^® aerosol foam (Cal/BD foam). Cal/BD aerosol foam has improved skin penetration and is reported to be better accepted by patients, relative to Cal/BD ointment or gel.¹⁰ Switching to Cal/BD foam can improve disease control. Significantly more patients using Cal/BD foam achieved a 2-grade improvement according to the physician’s global assessment of disease severity, with their psoriasis being clear or almost clear, by week 4 compared with patients using Cal/BD gel by week 8 (38.3% vs. 22.5%, respectively; P < 0.001).^11,12 Given that the active ingredients are the same, comparisons between the products relate purely to formulation.

In this study, medical records of Canadian psoriasis patients who transitioned from Cal/BD ointment or gel to Cal/BD foam were examined retrospectively. The objective was to explore Canadian dermatologists’ reasons for changing topical treatment formulation in these patients and to assess reasons the transition was judged successful or unsuccessful. As patients on topical monotherapy may have different motivations for and success with treatment transition, compared with those receiving concomitant topical and non-topical therapies (i.e., systemic treatment or phototherapy), the study included patients from both populations.

Patients and Methods

In this retrospective chart review, 9 Canadian dermatologists reviewed the medical records of their patients with plaque psoriasis who were previously treated with Cal/BD ointment or gel and were switched to treatment with Cal/BD foam. The study protocol was approved by RRB (Research Review Board Inc., Waterloo, ON, Canada; approval # 2019.538). The need for informed consent was waived due to the retrospective design of the study.

The dermatologists reviewed the medical records from their 10 most recent patients meeting all inclusion criteria: ≥18 years of age, with active psoriasis, and transitioned from Cal/BD ointment or gel to Cal/BD foam at the baseline visit (defined as the visit where the change in treatment occurred). Patients could not have made any change in prescribed systemic treatment or phototherapy from 3 months before to 1 month after the switch to Cal/BD foam. Baseline findings were from the visit during which the dermatologist first prescribed Cal/BD aerosol foam. Follow-up data were from the first subsequent visit, no less than 4 weeks and no more than 32 weeks after the baseline visit.

Using the data collected from the medical records, the dermatologists completed an online questionnaire developed from a pilot study carried out by 3 authors of the current study. The pilot study sought to identify classes of data that could be reliably found in medical records for psoriasis patients seen in normal Canadian dermatology practice. Pilot study data were not included in the current report.

Demographic and clinical characteristics extracted from the baseline visit records included age, gender, symptoms affecting quality of life, the dermatologist’s reasons for transitioning the patient to Cal/BD foam, the number of clinic visits in the 12 months prior to baseline, and history of psoriasis therapies in the 24 months prior to baseline. Patients were considered to be on topical monotherapy if they were using Cal/BD ointment or gel with or without other prescription or non-prescription topical agents, but without systemic treatment or phototherapy. Conversely, patients were considered as on combination therapy if they were using Cal/BD ointment or gel concomitant with phototherapy or systemic therapy. Physicians submitted their findings for each patient electronically until they had completed 10 reports. After the seventh report of patients in one class of treatment (topical monotherapy or combination therapy), the physician received an automatic reminder that both classes should be represented among their 10 reports.

The dermatologist’s assessments of psoriasis severity, as noted in the medical records, for the patient’s lifetime worst severity, severity at baseline, and severity at follow-up, were reported in the questionnaire using a 5-point scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe). Estimated percent body surface area (BSA) affected by psoriasis was extracted from the baseline and follow-up visits. The dermatologist’s assessments of improvement in quality of life, the impact of Cal/BD foam on overall psoriasis disease and itch or itch-related sleep loss, and whether the transition to Cal/BD was successful, were extracted from the records of the follow-up visit. Improvement in quality of life was rated on a 4-point scale (0 = no improvement; 4 = significant improvement). The level of impact on overall psoriasis disease and itch or itch-related sleep loss was rated as ‘Worsened’, ‘Same’, ‘Improved’, or ‘Resolved’. Dermatologists were asked to identify one or more specific signs or symptoms with the greatest impact on quality of life. If the patient’s record did not include the relevant information, dermatologists indicated ‘Unknown/Not documented’.

Descriptive statistics were analyzed using Microsoft^® Excel for Mac version 16.40 and reported as mean ± standard deviation (SD), median (range), and proportions. Missing data were not imputed, and the results for each variable were reported based on the number of patients for whom data were available.

Results

Nine dermatologists completed questionnaires for 10 patients each. Of those 90 questionnaires, 9 were excluded, leaving 81 patient records for analysis. Reasons for exclusion were that insufficient data were included (n = 1), Cal/BD foam was not used between baseline and follow-up (n = 4), and the follow-up visit was not within the 4 to 32-week timeframe (n = 4).

Baseline demographic and clinical characteristics are shown in Table 1. More patients were on monotherapy than on combination therapy. Psoriasis at lifetime worst was less severe in patients on topical monotherapy vs. combination therapy. The most commonly affected body areas were the legs, arms, trunk, and scalp.

Complete data for psoriasis severity (at worst, at baseline, and at follow-up) were available for 72 patients (Figure 1); with the remainder missing data from at least one of those time points. In those patients with complete data, severity at worst was mild or moderate in 36 (50%) patients. At baseline and at follow-up, 53 (74%) patients and 62 (86%) patients, respectively, experienced mild or moderate disease.

Patients who had experienced severe, or very severe psoriasis at its worst, were more likely to be on combination therapy and had greater baseline psoriasis severity and BSA affected, relative to those with mild or moderate psoriasis at worst (Table 2). For patients with severe or very severe disease, scaling, itch or itch-related sleep loss, and redness were identified as the signs and symptoms with the greatest impact on the quality of life. Among patients with mild or moderate psoriasis at worst, itch or itch-related sleep loss had the greatest impact on the quality of life. Similarly, redness had the greatest impact on quality of life for 8 of 14 (57%) patients on combination therapy but 3 of 14 (21%) patients on monotherapy, whereas itch or itch-related sleep loss had the greatest impact in 10 of 14 (71%) patients on monotherapy but 7 of 14 (50%) patients on combination therapy.

The most common reasons cited for transitioning to Cal/BD foam were to improve clinical efficacy (74/81; 91%), quality of life (49/81; 61%), and treatment adherence (41/81; 51%). These reasons were ranked similarly for patients on monotherapy and on combination therapy (data not shown).

In patients for whom data were available at both baseline and follow-up, median psoriasis severity score (range) was 2.0 (1.0-4.0) at baseline and 1.0 (0.0-4.0) at follow-up. Median BSA was 4.0 (1.0-45.0) at baseline and 1.5 (0.0-25.0) at follow-up. The median and overall ranges for psoriasis severity and BSA were similar for patients on mono- and combination therapy. These findings were comparable across all 9 dermatologists’ patient sets.

At follow-up, quality of life as assessed by the investigator had improved for 79% and worsened for 4% of the 80 patients for whom quality of life data were reported (Figure 2A). Improvement was also experienced by 5/10 (50%) patients for whom stigma was reported as having a major impact on quality of life. Itch or itch-related sleep loss resolved in 33% and improved in 54% of patients overall (Figure 2B). Of note, very similar improvements were observed for both quality of life and itch/itch-related sleep loss measures in subsets of patients who cited those specific respective factors as the reason for seeking to transition. Overall, disease resolved in 16%, improved in 66%, and stayed the same in 15% but worsened in 3% of patients (n = 79) at the follow-up visit.

In each category of psoriasis severity at baseline, at least half of patients experienced improved quality of life, improved or resolved overall disease, and improved or resolved itch or itch-related sleep loss (Table 3). When grouped by baseline severity, the proportions of patients showing improved quality of life (mild: 15/17, 88%; moderate: 33/40, 83%; severe/very severe: 12/20, 60%) and improved itch or itch-related sleep loss (mild: 11/17, 65%; moderate: 20/40, 50%; severe: 11/20, 60%) were highest for the mild severity patients but roughly similar across groups; the study was not powered to draw any conclusions with respect to improvement according to baseline severity.

Transition was considered successful in 69 of 81 (85%) patients. Of the 12 patients for whom transition was deemed unsuccessful, 7 needed systemic treatment, including biologics (3 and 4 patients on monotherapy and combination therapy, respectively), and no improvement was seen in 2 (1 on monotherapy; 1 on combination therapy). In addition, 1 patient disliked the cosmetic features of the aerosol foam; for 2 patients, no reason was cited. The most common reasons cited for considering transition successful were that the patient reported success (40/69; 58%), signs and symptoms of psoriasis had cleared at follow-up (32/69; 46%), and the patient continued to fill prescriptions (22/69; 32%).

Discussion

In this retrospective chart review, the transition from a Cal/ BD ointment or gel formulation (Dovobet^®) to a Cal/BD foam formulation (Enstilar^®) was rated successful in most cases. The most common reason cited was patient-reported success, and most patients experienced improvement in the specific measure (e.g., itch or itch-related sleep loss) cited as a reason for wanting to transition. These findings are supported by results of a previous survey in which Canadian respondents generally rated Cal/BD foam as more pleasant cosmetically, relative to previously used topical products,^8,9 consistent with other data that foam products are well accepted relative to other formulations.⁶

Transition success in the current study did not appear related to whether the patient was on mono- vs. combination therapy, as similar benefits were found in both groups. These benefits included improvements in overall disease, quality of life, and itch and itch-related sleep loss.

Itch is a pervasive challenge for psoriasis management, and itch severity is broadly associated with clinical severity.¹³ In this population, itch or itch-related sleep loss was reported in all severity groups. Following transition to Cal/BD foam, most patients with mild disease at baseline, as well as approximately half of others, experienced improvement or resolution of itch or itch-related sleep loss. Resolution was reported at a similar rate in the overall population and in patients for whom itch control was identified as a reason for treatment change. Given the clear disease burden associated with itch, dermatologists should ask their patients about their experience of itch and itch-related sleep loss, regardless of overall disease severity, and they should consider a change of topical treatment regimen in those who are dissatisfied with their current level of itch control.

Strengths and Limitations

This was a retrospective chart review of individuals transitioning between topical formulations, namely Cal/BD ointment or gel, to Cal/BD foam. The population may not be fully representative of Canadian psoriasis patients under a dermatologist’s care, since it would be expected to disproportionately include patients who are unsatisfied with Cal/BD gel or ointment. Due to the absence of a control group, no firm conclusions can be drawn regarding changes in symptoms of psoriasis related to the use of Cal/BD foam. For similar reasons, the findings here may not be generalized to other topical formulation transitions, including other transitions to foam formulations.

Conversely, strengths of this study include the real-world setting of treatment and the fact that the questionnaire used was developed through a pilot study that helped ensure that sufficient data could be captured for most variables of interest. It is also reassuring to note that the 9 physicians reported similar levels of treatment success among their individual patient sets, suggesting that the questionnaire was reliable and transparent to the respondents.

Conclusion

The benefits of transitioning from Cal/BD ointment or gel to aerosol foam formulation in this Canadian patient population were similar to those reported in clinical studies and were seen consistently among patients with a range of treatment priorities and with differing history of psoriasis severity and treatment history. Changing the topical treatment formulation, even without a change in active ingredients, should be considered for patients who are dissatisfied with their current topical treatment, independent of their psoriasis severity.

Acknowledgements

The authors thank the dermatologists who participated in the survey, Alice Kowalczyk, PharmD (LEO Pharma Inc. Canada) and Kristel Bermejo, PhD (imc North America, integrated medhealth communication) for contributing to the study design, and Celeste Lavallee, MSc (imc North America, integrated medhealth communication) for contributing to the data analysis and writing the article.

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¹McMaster University, Hamilton, ON, Canada
²Baywood Dermatology, Ajax, ON, Canada
³CCA Medical Research, Ajax, ON, Canada
⁴St. Michael’s Hospital, Toronto, ON, Canada
⁵Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
⁶Probity Medical Research, Waterloo, ON, Canada

Conflict of interest:
BC has no conflicts to disclose. DNA has been an advisory board member, investigator, speaker, consultant, or received honoraria from AbbVie, Actelion, Amgen, Boehringer, Celgene, Coherus, Dermira, Eli Lilly, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant.

ABSTRACT
Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.

Key Words:
enzyme replacement therapy, Fabry disease, alpha-galactosidase A, symptoms, treatment

Introduction

Fabry disease (FD) is an X-linked lysosomal storage disease, affecting glycosphingolipid metabolism. The cause of FD is a variety of mutations in the GLA gene on the X chromosome (Xq22.1), resulting in a deficiency of the lysosomal enzyme alpha-galactosidase A (AGAL). This leads to the progressive accumulation of globotriaosylceramide (GL3) in cells throughout the body, causing multi-systemic effects.¹ The incidence of FD in the general population is estimated to be 1:117,000.²

Presentation

The classical variant of FD results from a complete loss of alphagalactosidase A function. Its symptoms include acroparesthesia, sweating abnormalities (hypo/hyperhidrosis), cornea verticillata, and angiokeratoma, as well as cardiovascular, cerebrovascular, and renal disorders such as cardiomyopathy, arrhythmia, stroke, and proteinuria.¹ Non-classical or atypical variants of FD involve residual enzyme activity. Symptoms are generally milder, may be restricted to one organ, and have a later onset of 40 to 60 years of age. The severity of FD also depends on sex, with males being more severely affected than females.³ FD in heterozygous females has a wider spectrum, likely due to lyonization, where one X chromosome is randomly inactivated in female embryos.⁴

Facial dysmorphism has also been described in FD. The “Fabry facies” is characterized by periorbital fullness, bushy eyebrows, recessed forehead, pronounced nasal angle, bulbous nasal tip, prominent supraorbital ridges, shallow midface, full lips, prominent nasal bridge, broad alar base, coarse features, posteriorly rotated ears, and prognathism. Although there is no single facial feature to characterize FD, it is possible that these facial features may become more prominent with age due to the accumulation of GL3. Non-facial physical features that may indicate FD include broad fingertips, short fingers, and a small anterior-posterior chest diameter.⁵

Other Signs and Symptoms

Pain

The incidence of pain in FD has been reported in 81.4% of male patients and 65.3% of female patients. The average age of onset of pain has been found to be 14.⁸ years for males and 19.8 years for females.⁶ Pain is possibly caused by the deposition of GL3 in the dorsal root ganglia and sympathetic ganglia, or by small fiber neuropathy. Generally, the pain is either chronic or episodic. Episodic pain in FD, termed “Fabry crises,” typically begins in the extremities and radiates proximally, and may be triggered by exercise, illness, temperature changes, or other physical and emotional stresses. This neuropathic pain is also associated with a lack of temperature perception.⁷

Sweating Abnormalities

Hypohidrosis is prevalent in FD patients, with reported incidence of 53% in males and 28% in females. Anhidrosis has been observed in 25% of males and 4% of females. Hyperhidrosis occurs less frequently, with 6% of males and 12.6% of females reporting this symptom.⁸

Cornea Verticillata

Cornea verticillata are whorl-like corneal opacities, resulting from changes in the subepithelial layers of the cornea.⁹ It is the most common ocular manifestation of FD, observed in 76.9% of females and 73.1% of males. Other less common ocular manifestations include vessel tortuosity and Fabry cataracts. Cornea verticillata may also be pathognomonic for FD, as its differential diagnosis only includes specific medications, such as amiodarone and aminoquinolines. However, it does not have predictive value with regards to disease severity.¹⁰

Angiokeratoma

Angiokeratoma (AGK) is the most common cutaneous manifestation of FD, and has been reported in 66% of males and 36% of females.⁸ In FD, AGKs appear as non-blanching, red to blue-black lesions ranging from 1 to 5 mm in diameter.¹¹

The age of onset for AGKs is typically 5-10 years in males.¹² The distribution of AGK in males with FD is mainly on the penis, scrotum, inner thighs, lower back, buttocks, and the umbilicus. In females, AGKs are mainly found on the trunk and limbs.¹¹ While patients with FD generally describe an increasing number of cutaneous lesions over time, no correlation has been found between age and the extent or number of lesions.⁸ It is possible older patients are more observant of their skin and, therefore, report more AGKs.

The distribution of AGKs in FD differs from AGK in other diseases. Angiokeratoma of Fordyce usually appears after age 30 and is found on the genitals, angiokeratoma of Mibelli generally presents on the extensor surfaces of hands and feet, and angiokeratoma circumscriptum naeviformis is concentrated on the trunk and extremities.¹, ¹³ Idiopathic AGK is also possible without any specific localization.¹³

Diffuse AGK has also been observed in other lysosomal storage diseases, including fucosidosis, sialidosis, GM1 gangliosidosis, galactosialidosis, beta-mannosidosis, Schindler disease type II, and aspartylglucosaminuria.¹, ¹¹

AGK histology reveals a vascular proliferation inside the papillary dermis. The overlying epidermis is acanthotic and orthokeratotic. The vascular channels are occasionally plugged with erythrocytes. Dermoscopy of AGK shows red to bluish black vascular lacunae
with clear borders. Occasionally, overlying yellow keratotic areas are also observed.¹¹

Currently, it is unclear whether AGK can be used as a biomarker for disease progression or as a measure of efficacy of enzyme replacement therapy.¹⁴ However, when stratified by age, male and female FD patients with cutaneous vascular lesions (angiokeratomas and telangiectasiae) were shown to more likely have major organ involvement.⁸

Telangiectasia

Telangiectasia is reported to be the second most common cutaneous symptom of FD.⁸ In FD, telangiectasias are found on the face, lips, oral mucosa, and photodamaged areas such as the V of the neck.¹¹

Differential Diagnosis

For both males and females, at least one of the following is required for a definite FD diagnosis: FD-specific distribution of AGK or neuropathic pain, cornea verticillata, or increased plasma GL3. For males, a GLA mutation resulting in less than 5% leukocyte AGAL enzyme activity is also required for diagnosis. Family history of FD can be predictive, and urinalysis can be used to detect proteinuria. However, in the presence of a non-FD-specific distribution of AGK, pain, or cornea verticillata, and a GLA mutation of unknown significance, a definitive FD diagnosis cannot be established and alternative diagnoses should be considered.¹³

Dermoscopy can identify multiple lesions when they are not visible to the naked eye or when multiple AGKs are surrounding one distinct lesion.¹¹

Enzyme Replacement Therapy

Standard treatment for FD is enzyme replacement therapy (ERT). Currently, there are two forms of recombinant alpha-galactosidase A: agalsidase alfa, which is produced by continuous human cell lines, and agalsidase beta, which has been produced by Chinese hamster ovary cells transduced with the AGAL gene. According to a 2016 Cochrane Review, ERT has been shown to significantly alleviate the cardiac, renal, and neuropathic effects of FD.¹⁵ The US FDA has only approved agalsidase beta for FD,¹⁵ whereas both agalsidase alfa and beta are approved for FD in Canada. The Canadian Fabry Disease Initiative is a nation-wide study that is currently comparing the efficacy of the two ERT treatments.¹⁶ The recommended dose is 0.2 mg/kg of body weight administered every 2 weeks for agalsidase alfa and 1 mg/kg of body weight every 2 weeks for agalsidase beta.¹⁵

Six randomized controlled trials (RCT) examining the effect of agalsidase beta on skin GL3 deposition have been performed. A 20-week long RCT in 1999 involving 58 patients with skin-GL3 deposits as a secondary endpoint found significantly lower GL3 deposits in skin, kidney, and heart biopsies, with 20 of 29 patients who received treatment experiencing clearance of renal capillary endothelial GL3 deposits (a score of 0 on a scale of 0-3).¹⁷ In the subsequent 6-month open-label study, all patients in the former placebo group and 98% of patients in the former treatment group had scores of 0.¹⁸ In the same cohort of patients enrolled in an open-label trial, complete clearance of GL3 skin deposits was reported in 98% of patients at 30 months and 86% of patients at 54 months.¹⁹ Another RCT involving the same cohort examined dermatologic biopsies and found similar results, with scores of 0 (GL3 clearance) in superficial dermal capillary endothelial cells in 100% of adult patients, in deep dermal vascular endothelial cells in 85%, in vascular smooth muscle cells in 33%, and in the perineurium in 4%.²⁰ A 48-week open-label study from 2002 to 2005 with patients aged 8 to 16 years found clearance of GL3 deposits in superficial dermal capillary endothelial cells at 24 and 48 weeks, and a reduction from moderate/severe GL3 accumulation to mild/cleared GL3 accumulation in deep dermal capillary endothelial cells at 24 and 48 weeks.²¹ Another openlabel study from 2003 to 2006 examining skin and kidney GL3 deposits administered the standard dose of 1 mg/kg every 2 weeks of agalsidase beta to 21 adult patients for 6 months, and then a reduced dose of 0.3 mg/kg every 2 weeks for 18 months. Ninety-five percent of patients had a score of 0 (no GL3 skin deposits) at week 24, compared to 24% at baseline. During the low dose period, only 70-80% of patients had scores of 0, with seven patients experiencing increasing scores and two patients experiencing new spontaneous AGK.²²

A retrospective analysis involving 134 adult patients investigated the effects of immunoglobulin G (IgG) antibodies against agalsidase beta during treatment. No correlation was found between IgG titers and the onset of clinical events, renal function, or plasma GL3. However, a correlation was found between IgG titers and GL3 deposits in dermal capillary endothelial cells, with a larger proportion of patients with GL3 deposits in the highest titer subgroup.²³ The clinical significance of the possible effect of these antibodies is still unknown.

Conclusion

FD is a multisystem X-linked lysosomal storage disease. The most common cutaneous manifestation is diffuse angiokeratomas. Family history of FD and common symptoms, including cornea verticillata, neuropathic pain, and sweating abnormalities, can be used to confirm an FD diagnosis. ERT has shown to be an effective form of treatment to alleviate cardiac, renal, and cutaneous effects of FD. Overall, dermatologists should always consider FD as a potential diagnosis in the presence of angiokeratomas, and ERT administered promptly upon confirmation of FD as the causative disease.

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