Literature search strategy and study selection

A systematic search of the literature was conducted for this review using the computerized bibliographic databases PubMed, Embase, PsycINFO and Web of Science. All databases were searched for English articles published from January 1, 2000 until July 6, 2020. The search procedure was conducted and documented according to PRISMA guidelines for systematic reviews.¹⁰ The search included keywords related to ‘cutaneous T‐cell lymphoma’, ‘Mycosis fungoides’, ‘Folliculotropic mycosis fungoides’, ‘Sézary syndrome’ and ‘quality of life’. The detailed search strings are outlined inSupplementary material.

Inclusion and exclusion criteria

We included only original articles that fulfilled our inclusion criteria. Studies were included if they described the quality of life in patients with MF and/or SS retrieved by questionnaires or qualitative interviews. In case of studies describing the effect of an intervention, only the QoL data at baseline were included in the results. If study populations involved less than 15% of patients with other types of CTCL, these data were also included. Studies with <5 patients, patients aged <18 years, reviews, letters and comments without aggregated data were excluded.

Data collection process

Titles and abstracts of retrieved articles were independently screened by two authors (RO and KQ) for inclusion criteria. If there was disagreement between the two authors, the opinion of a third author was decisive (MV). Subsequently, the full text of potentially relevant articles were assessed for eligibility by the same two authors. After the full text screening, the references of the included studies were manually screened for additional eligible articles.

QoL data were reported for several stages of CTCL if possible; early stage MF (stage IA‐IIA), late‐stage MF (stage IIB‐IVB), SS and mixed stages MF/SS.

In case of a mix of CTCL stages, undefined stages of disease or in case that no separate QoL results were reported per disease stage, the results of that particular study were reported under mixed stages MF/SS.

The following study characteristics were extracted from the included studies: year of publication, country, sample size, age of population, CTCL diagnosis, disease stage and reported CTCL stages. The reported QoL measurements were extracted from (validated) questionnaires and qualitative interviews. In addition, if studies also described other outcomes, such as severity of pruritis, depression, anxiety and illness perception, this was also extracted and correlated to the measured QoL from questionnaires. Furthermore, if included studies compared QoL results to other diseases or general population, these were also reported separately.

No formal meta‐analysis with pooling of results was performed, as it was expected that the included studies would have a high degree of heterogeneity of study populations with regards to staging and extent of disease, prior and current therapies, and varying points of time of conducting the outcome measurements. Due to the lack of homogenic data, this was of no additional value.

Methodological results

A total of 317 studies were found and screened for eligibility. Details of the selection process for eligible studies are shown in Figure 1. In total, 24 studies matched the eligibility criteria.⁵,⁶,¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹,³² All included studies were published between 2001 and 2020. The sample size ranged from 5 to 630. In total, 21 studies used QoL questionnaires and four studies used qualitative interviews.⁵,⁶,¹¹,¹²,¹³,¹⁴,¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹,³² Of these studies, one study used both QoL questionnaires and qualitative interviews.³¹

QoL instruments

A total of 18 different questionnaires were used to report on QoL. These concerned dermatology‐specific, cancer‐specific and generic QoL instruments. Furthermore, specific pruritus instruments were used in 7 of the included studies. A brief description of the used instruments is provided below and a complete overview of the used instruments per study is displayed in Table 1.

Dermatology‐specific QoL instruments

Cancer‐specific questionnaires

Generic QoL instruments

Generic instruments for specific symptoms and illness perceptions

Qualitative studies

Qualitative studies were included in order to report QoL related outcomes that were not addressed in the standardized QoL instruments. In case, both qualitative outcomes and standardized QoL instruments were assessed, the results of both methods were reported.

Quality of life results

Early stage disease

The great diversity in severity of the disease was also reflected by the degree of affected QoL across the various stages of the disease. Although it was found that even in patients with a limited disease (early stage MF), the QoL was significantly affected.¹⁸,²³,²⁴,²⁸

Late‐stage disease (MF/SS)

Late‐stage disease was found to have a greater effect on the QoL\x92than early stage disease.(15, 18, 22, 23, 25, 26, 28, 53; Table 2,3,4,5).

Erythrodermic MF/SS

Only two studies reported separate results for patients with SS or erythrodermic MF (Table 1).¹²,¹³ QoL was the most affected in this group of patients (Table 3 and5).

Mixed stages MF/SS

Twelve studies described cohorts of patients from stage IA‐IVB/SS without reporting separate aggregated data per disease stage (Table 1).

Comparison to other diseases and general population

Multiple studies compared QoL scores of MF/SS with other dermatologic and non‐dermatologic diseases.⁶,¹³,¹⁹,²²,²⁵,²⁶ As the QoL was very dependent on the degree of early‐ and late‐stage disease, the comparison of QoL scores to other diseases also varied.

Patients with relatively mild disease had QoL scores comparable with psoriasis and vitiligo with regards to emotions and functioning, but experience more QoL impairment due to symptoms.²⁵ Molloy et al. and Holahan et al. also suggested that early stage MF is comparable with acne vulgaris, atopic dermatitis, contact dermatitis and psoriasis. SS is more severe with much higher scores than benign dermatoses and non‐melanoma skin cancer.¹⁹,²² However, Steinke et al. showed that dermatologic QoL in MF patients was more affected than in patients with atopic dermatitis, psoriasis and prurigo nodularis.²⁷

Furthermore, compared to various other chronic conditions such as cancer or dermatitis, SS patients had a significantly lower mean physical component.¹³ Overall, QoL measured with HUI‐3 was lower in MF/SS than scores associated with patients with diabetes.²⁶

General quality of life compared to healthy controls was significantly more affected in MF/SS.⁶,¹³ Compared to a sex‐ and age‐adjusted general population, patients with SS had lower general health, lower physical functioning, lower social functioning and lower vitality levels.¹³

Compared to a matched healthy control group the mean depression and anxiety scores for patients with MF/SS were significantly lower.²⁶

Association between pruritus and QoL

There were seven studies that described dermatology‐specific, generic or cancer‐specific QoL, as well as the degree of pruritis (Table 3).¹²,¹⁷,¹⁸,²⁰,²¹,²⁷,²⁸ For early stage disease the skin specific QoL was relatively mildly affected, with pruritus scores of 3.3 (±3.0) and 2.8 (±3.1).¹⁸,²⁸ For late stage, the dermatology‐specific and generic QoL was more severely affected and more intense pruritis were found. In the studies describing mixed stage disease, the pruritis scores seemed higher in the studies that described a lower QoL.¹⁷,²⁰,²¹,²⁷,²⁸ Steinke et al. reported that 42% of the patients indicated that their QoL was often or always affected because of itching. The itchy‐QoL scores of MF indicated that the pruritus affected QoL was similar to that of atopic dermatitis and psoriaris vulgaris.²⁷

Qualitative studies

Four studies reported results of a qualitative analysis based on (semi‐structured) interviews in patients with early and advanced stage CTCL (Table 1).²⁹,³⁰,³¹,³²

A recurrent theme was that a significant proportion of the patients felt that an earlier diagnosis might have reduced the spread of the disease. In the study of Bhat et al., 72% of patients reported that their skin disease was initially mistaken for psoriasis or eczema.³⁰,³² After the diagnosis was made, the rarity and lack of public understanding of the disease were frustrating to many patients.³⁰,³¹ Diagnosis could be shocking and frightening and there were descriptions of being ‘devastated’ or ‘dumbfounded’. Furthermore, anxiety was associated with a diagnosis of cancer or a name that sounded like ‘a fungus’.²⁹ Patients often had to correct or accommodate the misperception of their disease being contagious.³⁰

Symptoms reported in the qualitative studies (i.e. itch, hair loss, pain, fatigue) were in accordance with previously mentioned quantitative studies. Pruritus was the most bothersome symptom, regardless of disease stage.³¹ One of the most important ways in which itching affected patients daily lives was in their ability to sleep.²⁹,³⁰,³¹ Overheating and discomfort were mentioned often and were reasons for no longer sharing a bed with their partner.²⁹

Managing skin flaking was particularly effortful and time‐consuming, with extensive routines regarding bathing, applying topical therapies and adjusting their clothing for comfort and minimizing embarrassment.²⁹,³⁰,³¹

MF and SS also resulted in limitations in practical daily life activities. Twelve out of 19 patients in the study of Demierre et al. (2011)³¹ reported difficulty with travel by public transport or car due to painful or sensitive skin. Lack of energy prevented patients from accomplishing tasks at work and at home and secondary inability to concentrate due to fatigue or itching.³⁰ In the study of Demierre et al. (2011), 31% of patients desired to participate less in social activities since the diagnosis.³¹

Despite the symptom burden and its impact, participants described effective coping strategies. Central to these was drawing on emotional and practical support from family and friends.²⁹,³² Practical support included everyday assistance with application of topical agents, driving, accompanying to appointments, and help with household chores that patients were no longer able to do.²⁹ The disease also had a profound effect on caregivers.³² Caregivers fulfilled multiple roles; acting as healthcare advocates, communicating with others about the patient’s condition, attending appointments, providing medical and physical care (related to wounds and injections) and psychological support, housework and driving. A striking theme was the effect of CTCL on the relationship, communication and intimacy between caregiver and patient. Finally, patients also noted substantial treatment and financial burden.

Limitations

Due to the heterogeneity in study populations, disease stages and used QoL instruments, pooling of data was not possible and the outcomes must be interpreted with caution. However by describing separate results for the different stages of disease, a practical overview of the current literature was provided that has not been described in the literature previously.

Furthermore, some results included in this review were based on variables not included as search terms in our systematic search. This was done in order to be able to report how different variables (e.g. pruritus) were correlated with QoL. As pruritis was the most frequent symptom reported by the QoL instruments, these data provide an additional insight. However, future studies should corroborate these results and minimize the possible influence of selection bias.

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Supplementary Materials