Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Cutaneous T Cell Lymphoma

Abstract

Cutaneous T cell lymphoma and its subtypes, mycosis fungoides (MF) and Sézary syndrome (SS), comprise a spectrum of chronic lymphoproliferative disorders in which neoplastic T cells accumulate within the skin and visceral organs. This process is frequently characterized by severe pain, nonpain symptoms, and physical disfigurement. Significant emotional, spiritual, and existential distress is also felt by many of these patients as they experience a chronic, often incurable disease. Patients suffering from these diseases, though not commonly encountered, can benefit greatly from palliative care support. In this article, a team of palliative care clinicians, critical care physicians, and an oncologist specializing in lymphoma offer 10 tips to help palliative care teams to support these vulnerable and often-distressed patients and their caregivers.

Introduction

Cutaneous T cell lymphoma (CTCL) is a heterogeneous spectrum of lymphoproliferative disorders in which neoplastic T cells accumulate within the skin, with potential involvement of lymph nodes, blood, and visceral organs. Approximately 20,000 patients in the United States carry this cancer diagnosis, with ∼1200 new cases diagnosed yearly.¹ Overall, the incidence of CTCL in the United States is ∼10.2 per million people, with rates highest in patients who are older, male, and Black.²

The most common CTCL subtype is mycosis fungoides (MF), with an incidence of ∼5.6 per million people.² Sézary syndrome (SS), its leukemic variant, is the second most common subtype, affecting ∼0.1 per million people.^3,4 Both conditions predominantly involve the skin, leading to patches, plaques, and skin tumors. They may also affect extracutaneous organs including viscera, lymph nodes, and blood. Each CTCL subtype is diagnosed based on histopathology and clinical features, and each is a chronic illness; other than allogenic hematopoietic stem cell transplantation in select patients, no curative options exist.³

Overall survival correlates with disease stage at diagnosis.^5,6 The majority of patients with MF are diagnosed at an early stage, with 71% having disease limited to the skin.⁶ Patients with early stage disease have a more favorable prognosis. The development of frank tumor growth on the skin (i.e., tumor-stage disease) and involvement of lymph nodes or blood are adverse prognostic factors and represent more advanced stages of MF.^5,6

Patients with tumor-stage disease, lymphatic, or blood involvement have worse survival relative to matched control patients, with median overall survival of 1.5–4.0 years.^5,7 More advanced disease correlates with more significant impairments in health-related quality of life.^1,8 Treatment of early stage disease typically involves skin-directed therapies and/or phototherapy and radiation therapy, whereas refractory early stage and advanced disease is treated with systemic therapy.⁹ Treatment decisions are patient-specific without standard protocols, and multiple medical disciplines may be involved in decision making.

Although CTCL is a rare diagnosis, it is important that all palliative care (PC) clinicians at large cancer centers and elsewhere are aware of the unique needs of this patient population. Owing to extensive skin involvement, CTCL can cause profound pain and distress, and presents a multitude of challenges for oncology, dermatology, and PC team members caring for these patients. As an interdisciplinary, interprofessional group caring for these patients at a dedicated cancer center, we have compiled 10 tips to highlight the important PC needs of patients with CTCL and their informal and professional caregivers.

Tip 1: Many CTCL Patients Experience Delays in Diagnosis and Therefore in Care, Which Can Erode Their Trust in Clinicians and the Medical System

CTCL often presents with nonspecific dermatological manifestations, such as erythematous plaques, patches, and tumors. Erythroderma, when confluent lesions affect 80% of a patient's body surface area, may also be a feature. Other nonspecific findings include alopecia, hypopigmentation, keratoderma, redundant skin folds, and blistering,¹⁰ many of which resemble more common and less severe dermatological processes, such as atopic dermatitis, psoriasis, and vitiligo. Associated laboratory findings are also nonspecific. Therefore, the diagnosis of CTCL cannot be made on physical examination alone and requires correlation with a detailed clinical history and skin biopsy.

A skin biopsy revealing lymphoid infiltrate with atypical lymphocytes, when correlated with immunopathology and molecular evaluation of T cell clonality, confirms a CTCL diagnosis.^3,11 However, in certain cases, the high number of inflammatory cells may interfere with identification of tumor cells, and a patient may require multiple skin biopsies before a diagnosis is made.¹⁰ Some patients require further diagnostic evaluations, including positron emission tomography-computed tomography (PET/CT) and lymph node biopsy, to confirm staging.

The median age at diagnosis with CTCL is in the late 50s or early 60s.¹² However, a small proportion of patients with CTCL may be diagnosed in childhood or adolescence. There are also case reports of CTCL affecting very young children, including infants.¹³ In MF, 0.5%–7% of cases may be diagnosed in childhood.¹⁴ MF in childhood can be misdiagnosed as a more common pediatric dermatological condition, such as atopic dermatitis or ringworm. Most cases in this age group are early stage with mild features; however, a delayed diagnosis is associated with a poorer prognosis.¹⁴

Given the mentioned challenges, it can take months to decades for clinicians to accurately diagnose CTCL.^15,16 Delays in diagnosis may lead to patient anger and frustration.¹⁷ Clinicians should recognize the prolonged diagnostic process that patients may have experienced before receiving their CTCL diagnoses and bear in mind that this may generate mistrust toward the medical system.

Tip 2: Patients with CTCL May Experience Debilitating “Total Pain” Encompassing Physical, Psychological, and Existential Dimensions, and the Burden of Suffering May Disproportionally Impact Certain Sociodemographic Groups

Patients with CTCL experience multifaceted distress that extends far beyond the physical domain alone. In addition to the physical pain reported by ∼50% of patients,¹ patients often describe significant psychological and existential stressors associated with CTCL. Painful swollen skin and joints may interfere with their ability to participate in activities that they typically enjoy.¹⁷

One national survey of 630 patients with CTCL showed that 66% reported fatigue or impaired sleep, impeding daily activities in 50% of patients and causing 55% to miss school or work.¹ CTCL hindered the ability of 43% of patients to meet family needs, and 61% of patients reported financial stressors throughout the illness.¹ A majority of patients (62%) reported feeling unattractive and 39% experienced shame related to their skin condition.¹ Nearly half (47%) of patients reported interference with sexual intimacy or ability to be close with loved ones.¹ Over half (63%) reported that their skin condition influenced their choice of clothing, and >80% struggled with pruritus (88%), scaling (83%), and erythema (94%).¹ Almost all patients reported concerns about the seriousness of the disease and 80% worried about their mortality.¹

Recent evidence illustrates that the burden of suffering in MF/SS may vary according to other sociodemographic factors such as patient age, gender, race, and type/stage of illness. For example, quality of life measures are worse in CTCL patients who are Black, female, younger, and/or have more advanced stages of MF/SS.¹⁸ Further research is needed to thoroughly investigate the nature and extent of PC disparities in CTCL, and to promote health equity and optimal comprehensive care within this vulnerable population.

Tip 3: Physical Pain from CTCL Is Often Extreme and Multifaceted, Warranting Specialist Expertise in Complex Cancer Pain Management

Physical pain in CTCL is produced by a variety of mechanisms that cause multiple manifestations. The predominant component is nociceptive pain originating from cutaneous lesions, plaques, and tumors. CTCL patients may also experience neuropathic pain in the setting of skin flaking,¹⁹ causing sensations of burning, itching, stinging, and irritation.⁸ First-line treatment with nonopioid pain medications, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), is indicated for mild nociceptive pain in CTCL, but usually fails to provide adequate symptom relief for more severe nociceptive pain.

For neuropathic pain, gabapentinoids such as gabapentin or pregabalin may provide relief. Severe pain generally requires treatment with opioids, which may address both nociceptive and (to a lesser extent) neuropathic pain. Management of pain crises may require rapid opioid escalation, including the use of intravenous patient-controlled analgesia.²⁰ A combination of short- and long-acting opioids may be needed to address evolving pain needs, and early introduction of methadone may be considered for persistent pain and an anticipated continued need for opioids.

Patients may become increasingly tolerant to opioids and experience refractory pain. Some data and our clinical experience suggest that ketamine may be helpful when pain is poorly controlled by opioids despite appropriate dose escalation and rotation; in these cases, ketamine may be initiated as a multiday infusion with slow uptitration.²¹ Despite its growing use, high-quality evidence for ketamine's efficacy in the cancer population remains limited.^22,23

CTCL pain management can be most challenging during dressing changes, especially for areas of denuded skin. Ketamine, administered either as single doses by trained providers or as a continuous infusion as already described, may provide adjuvant analgesia for refractory pain in these circumstances. Benzodiazepines may be coadministered with opioids to treat anxiety associated with painful dressing changes. In extreme circumstances, palliative sedation may be necessary to achieve comfort during nursing and medical interventions.

Some of these patients continue to receive systemic cancer-directed therapy with the hope of mitigating the underlying disease process. In these situations, the expertise of an interprofessional, interdisciplinary PC team will help to mitigate distress as well as increase communication and shared decision making around care that is concordant with values in the context of symptoms and illness trajectory.

Tip 4: Nonpain Symptoms, Including Extreme Pruritis, Intensify the Suffering Associated with CTCL

CTCL also presents myriad nonpain symptoms, the severity of which tends to correlate with disease stage.²⁴ Pruritus is the most commonly reported symptom, and its treatment is particularly challenging due to limited understanding of the underlying etiology.²⁵ Pruritus may be secondary to an inflammatory process, making topical or oral corticosteroids reasonable approaches for palliation.^25,26 Unfortunately, pruritus secondary to CTCL is often refractory to antihistamines and topical corticosteroids.²⁵ Low-dose mirtazapine has been used as an antipruritic agent in CTCL^27,28 and may be especially beneficial when there is pruritus accompanied by impaired sleep and depression.²⁹ Research is ongoing regarding the role of mu-opioid receptor antagonist topical agents, such as naloxone lotion, in the management of pruritus associated with CTCL.²⁵

Other common symptoms in the course of CTCL include alopecia, impaired sleep, depression, fatigue, and changes in self-concept with accompanying emotions of shame and embarrassment.⁸ Such symptoms should be assessed and addressed as part of comprehensive care of CTCL patients, whether or not the patient is pursuing systemic cancer-directed therapies, and may include referrals to dermatologists, sleep specialists, and psychiatrists as clinically appropriate.²⁴

Tip 5: While Patients Facing Cancer Often Experience a Loss of Self-Identity, the Disfigurement Associated with CTCL Can Be Especially Distressing for Patients and Families

As skin involvement progresses from patches to plaques to nodular forms,¹⁶ the disease becomes more visible, and therefore more intrusive in the lives of patients and their families. Progression can trigger feelings of shame and embarrassment, disrupt patients' ability to be physically and emotionally intimate with loved ones, and strain relationships within families.^30,31 In a recent qualitative study, one patient reported, “I feel like what a leper must've felt like.”¹⁹

Other patients described “otherness” (feeling depersonalized or not like oneself), hopelessness, depression, and even suicidality as psychological consequences,¹⁹ consistent with the severe emotional impact of cutaneous diseases in general.³² In our team's experience, some patients with CTCL may question whether they are being “punished” by their disease and can suffer intense spiritual, existential, and psychosocial distress. To optimally care for these patients, clinicians must address not only the profound physical pain but also the broader suffering and collaborate with social work, mental health, and chaplaincy colleagues as appropriate.

Tip 6: Patients with CTCL Struggle with Complex Decision Making in the Context of Multiple Potential Treatment Paradigms Throughout the Illness Course

MF and SS are managed as chronic diseases by a multidisciplinary team including medical oncology, dermatology, radiation oncology, and—ideally—supportive oncology/PC. There is no standard first-line approach to treatment. Disease-directed treatment plans are individualized for each unique patient, with the goal of maximizing both disease control and quality of life based on each patient's personal goals and values.

Despite having a more favorable prognosis, patients with early stage disease may still experience significant psychological distress related to their cancer diagnosis, treatment, and potential for disease progression. Treatment of more advanced stage disease can incorporate one of several different systemic agents in combination with skin-directed treatments (e.g., topical steroids and phototherapy) or radiation to tumors or large areas of skin involvement. Goals of therapy must be discussed with the patient, accounting for treatment intensity, schedule, and duration.^33,34

Although not currently a standard therapy, allogeneic stem cell transplant is a potentially curative modality in select patients. This entails significant risks of morbidity and mortality, which must be carefully weighed against potential benefit in the context of each patient's clinical status and goals. Variable eligibility for clinical trials further complicates the decision making process for CTCL patients and families. Without a standard “best” treatment paradigm, PC consultants should be integrated early in the disease process to assist with person-focused decision making to support patients, families, and the health care team along the uncertain illness trajectory.

Tip 7: Families and Caregivers of Patients with CTCL Experience Intense Suffering

Informal caregivers often play crucial roles in caring for patients with CTCL, including attending medical appointments, aiding in skin care, providing psychological support, and advocating for their loved ones.³⁰ Family members report significant impact on their own quality of life, including emotional distress, physical and financial burdens associated with care, and impairments in social life.³¹ Communication challenges within the relationship and difficulty achieving intimacy are commonly reported difficulties as they witness their loved ones suffer.³⁰ In contrast, some family members also report that the experience of facing the disease together may strengthen their relationships and bring a family unit closer together.^17,30

Although patients with CTCL typically decline over a prolonged period, family members may still be surprised and overwhelmed at the time of death.³⁵ Clinicians must consider the physical, psychological, and spiritual needs of family members and informal caregivers, in addition to those of patients. Clinicians should utilize available resources to fully support caregivers throughout the illness and bereavement, including referral to local support groups and online patient and family discussion forums sponsored by national organizations.³⁶

Tip 8: Special Settings, Such as the Intensive Care Unit, May Be Required to Facilitate the Most Effective Analgesic Interventions While Ensuring Patient Safety

Patients with CTCL are at risk for serious malignancy-related complications including tumor lysis syndrome, hemophagocytosis, sepsis, and hypercalcemia,³⁷ any of which may lead to rapid multiorgan dysfunction and require intensive care unit (ICU) management. Like patients with severe burns, CTCL patients with extensive skin denudation may also develop life-threatening hemodynamic instability (including hypotension, tachycardia, and hypothermia), hypovolemia, and electrolyte derangements that accompany the loss of water and heat due to barrier disruption.

With or without critical illness, however, the ICU may be the optimal setting for the CTCL patient with needs for care, including analgesia and other supportive care, that require high-acuity monitoring and staffing. For example, patients requiring frequent skin evaluations and painful dressing changes benefit from the ICU's higher nurse-to-patient ratio and resources for safe administration of conscious sedation during these procedures. In some institutions, certified providers may be able to provide moderate sedation at the bedside on the wards.

In extreme situations, endotracheal intubation may be required for airway protection while administering high doses of opioids and benzodiazepines to alleviate patient distress. Possible ICU transfer is best embedded within a larger discussion about overall care goals, as well as available resources, and may involve multiple disciplines and caregivers along with the patient.

Tip 9: Nurses and Other Providers May Experience Extreme Distress from Bearing Witness and Contributing to Patients' Pain and Suffering

Clinicians providing care to CTCL patients may themselves suffer with the burden of bearing witness to patients' pain and distress. This is especially intense for those, such as nurses, who may need to perform interventions that are painful. One nurse recounted, “Patients have described living with CTCL as ‘being trapped inside my body’ from which there is never any escape.”³⁸ Patients sometimes share their anxieties, fears, and sadness with their nurses, with whom they may have particularly trusting relationships.³⁸

Nurses and others must also work within the patient's context of complex and strained family dynamics.³⁸ In addition, nurses help support CTCL patients as they attempt to navigate the loss of previously learned skills and abilities and acquire strategies for maintaining roles and aspects important to their identity. These critical responsibilities and experiences add to the demands of their basic clinical duties.

Clinicians in general, and nurses in particular, experience guilt accompanied by emotional and moral distress when they perform painful procedures such as dressing changes and skin care, even when these procedures are necessary to manage the disease and its complications. A patient may experience unbearable pain during a dressing change, despite aggressive periprocedural analgesic management. Over time, clinician distress can become extreme and debilitating. Strategies to mitigate distress include rotation of nursing assignments and regular debriefing sessions. It is the responsibility of the full team to recognize the unique challenges faced by nurses caring for CTCL patients at the bedside, provide peer support, and continue searching for new ways to alleviate the distress experienced by clinicians across professions and disciplines.

Tip 10: Close Interdisciplinary and Interprofessional Collaboration, Ideally Including Palliative Care Specialists, Is Crucial to Address the Multidimensional Distress Experienced by CTCL Patients, Their Loved Ones, and the Health Care Team

Given the intense, complex, and profound suffering that may be experienced by CTCL patients, their caregivers, and health care providers, it is important to integrate multiple disciplines and professions, including PC specialists, into a team-oriented approach. Medical oncologists contribute their expertise regarding the underlying illness process and its treatment, radiation oncologists share their input regarding the potential role for radiation therapies, and dermatologists help manage the cutaneous manifestations and complications of the disease.

Interdisciplinary PC team members, including physicians, nursing professionals, advance practice providers, social workers, chaplains, and pharmacists, all work together to support the oncological plan. At the same time, PC clinicians can focus attention on the physical, psychological, existential, and spiritual components of suffering experienced by patients and caregivers and the distress of the clinical team itself. In this collaborative manner, the multidimensional suffering of CTCL patients, their loved ones, and the health care team can be most comprehensively and effectively alleviated.

Conclusion

CTCL is a spectrum of rare cancers in which lymphomatous cells chronically accumulate in the skin and visceral organs, presenting myriad PC challenges. These include the management of debilitating physical symptoms and intense psychological and existential distress felt by patients and their loved ones. In the face of an uncertain illness trajectory and limited curative options, patients struggle with difficult decisions at multiple points throughout their disease. The clinical team, especially nurses, may also experience suffering and moral distress in caring for CTCL patients.

An early, systematized, interprofessional, and interdisciplinary approach to PC in CTCL can more fully address patients' profound suffering, while supporting patients to receive the most sophisticated and effective oncological treatment; particular attention should be paid to identification and amelioration of physical, emotional, and spiritual suffering of CTCL patients, their loved ones, and health care teams.

Funding Information

NK, JEN, MNW and AVD are supported by the NIH/NCI Cancer Center Support Grant P30 CA008748. AVD is supported by a Career Development Award from the National Palliative Care Research Center (Kornfeld Scholars Program) and was the Frances Young Tang Research Fellow in Palliative Medicine at Memorial Sloan Kettering Cancer Center from 2016 to 2017.

Author Disclosure Statement

No competing financial interests exist.