|Year : 2019 | Volume
| Issue : 1 | Page : 37-41
Sezary syndrome in a 65-year-old schizophrenic patient
Abdullahi Umar1, Tahir Turaki Mohammed1, Maryam Shehu Ahmed1, Modupeopla Omotara A. Samaila2, Hadiza Sani3
1 Department of Medicine, Dermatology/Infectious Disease Unit, Ahmadu Bello University, Zaria, Nigeria
2 Department of Pathology, Ahmadu Bello University, Zaria, Nigeria
3 Department of Medicine, Dermatology Unit, Barau Dikko Teaching Hospital, Kaduna, Nigeria
|Date of Web Publication||14-Feb-2019|
Dr. Abdullahi Umar
Department of Medicine, Dermatology/Infectious Disease Unit, Ahmadu Bello University Teaching Hospital, Zaria
Source of Support: None, Conflict of Interest: None
Sezary syndrome (SS) is the leukemic variant of cutaneous T-cell lymphoma characterized by a triad of erythroderma, peripheral lymphadenopathy, and the presence of circulating atypical lymphoid cells (Sezary cells) in the blood. We present a 65-year-old female with a recent-onset schizophrenia, presenting with a 3-year history of recurrent generalized pruritus, erythroderma, and a 2-month history of recent-onset, mushroom-like skin tumors. Examination revealed generalized erythroderma affecting more than 80% of total body surface area and significant peripheral lymphadenopathy. Peripheral blood buffy coat examination showed Sezary cells which constituted more than 18% of total circulating lymphoid cells, and histology report of the wedge biopsy of skin tumor confirmed mycosis fungoides. The patient was commenced on cytotoxic chemotherapy with some improvement in symptoms. However, she relapsed 2 months later, with development of new fungating tumors and died from overwhelming sepsis. We report this case to highlight the occurrence of two comorbidities together, each of which may negatively worsen the progression of the other, and to report a case of SS as one of the rare causes of generalized exfoliative dermatitis. Thus, there is a need for early skin biopsy and histology in any elderly patient presenting with recurrent generalized pruritus and erythroderma.
Keywords: Exfoliative dermatitis, mycosis fungoides, schizophrenia, Sezary syndrome
|How to cite this article:|
Umar A, Mohammed TT, Ahmed MS, Samaila MO, Sani H. Sezary syndrome in a 65-year-old schizophrenic patient. J Clin Sci 2019;16:37-41
| Introduction|| |
Sezary syndrome (SS) is the leukemic variant of cutaneous T-cell lymphoma (CTCL) characterized by a triad of generalized exfoliative dermatitis (GED) (now defined as affecting >80% of body surface area), lymphadenopathy, and the presence of 5% or more of malignant T-cells with cerebriform nuclei (known as Sezary or Lutzner cells) in peripheral blood lymphocytes. The disease was first reported in 1938 by Sezary and Bouvrain and then independently by Baccaredda in 1939. It is an aggressive and rare disease with 5-year disease-specific survival of <25%. The incidence of primary CTCL increases with advancing age, with a median age of 60–70 years, and the disease is rare in individuals <30 years of age. The disease has an overall incidence of 2.5% and affects men twice as women. There are three phases of developing mycosis fungoides (MF)/SS: (a) The premycotic stage, which can be localized or diffuse with superficial eczematous or erythematous lesions, (b) the infiltrative plaque stage, and (c) the tumor stage.
SS can be diagnosed by clinical history, physical examination, full blood count and differentials, peripheral buffy coat examination, and skin biopsy. Diagnosis was confirmed by immunohistochemical studies of CD4/CD5/CD8 and CD30.
| Case Report|| |
The patient is a 65-year-old female who was referred to the dermatology clinic from the psychiatric clinic, where she is managed for a recent adult-onset schizophrenia. She presented with a 3-year history of recurrent itchy skin, involving the scalp, face, trunk, and extremities. Itching was severe and worst at night to interfere with sleep. Initial physical examination revealed widespread scaly patches over the face, neck, trunk, and extremities with thick adherent and waxy scale over the scalp and some loss of scalp hair. There was associated lichenification, excoriations, and xerosis of the skin with postinflammatory depigmented, hypopigmented, and hyperpigmentary changes on the extremities. An initial assessment of chronic seborrheic dermatitis in a schizophrenic patient was made; she was placed on ketoconazole shampoo wash, ketoconazole cream, and chlorpheniramine tablets with some improvement in her symptoms.
Eight weeks after initial presentation, she presented again with worsening of her symptoms, with associated scaly erythema affecting most part of the skin. She was managed for erythrodermic seborrheic dermatitis with much improvement thereafter. However, a month later, during her subsequent visit, she had another flare of exfoliative dermatitis which was also managed with significant improvement.
Thirteen months after her initial presentation to the dermatology clinic while on routine follow-up, she presented again with another exacerbation of exfoliative dermatitis. There was associated multiple fungating ulcers over her back, right forearm, and left breast with worsening itching, noticed 2 months prior to presentation. Clinical examination at that time revealed an elderly woman with mild pallor, significant left axillary lymphadenopathy largest measures 4 cm × 4 cm firm, non-tender, and freely mobile. She has slight ectropion and loss of eyelashes with generalized alopecia. There was generalized xerosis with widespread scaling, fissuring on background erythematous skin, especially around the face. Has dystrophic nail changes with subungual hyperkeratosis. There were multiple ulcers with raised edges, mushroom-like, and discharging pus, over the left breast and back with necrotic base [Figure 1] and [Figure 2], largest on the back measuring 6 cm × 4 cm. She had no hepatosplenomegaly on abdominal examination. Other clinical examination findings were normal.
|Figure 1: A fungating mushroom-like tumor on the back, on background scaly erythematous plaques and patches|
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From her medical history, the patient presented to the psychiatric clinic 4 months before her referral to the dermatology clinic on account of 2-month history of irrational behavior, during which a diagnosis of functional schizophreniform disorder was made. She has been on haloperidol and Artane and was said to be regular on it.
The results of serum biochemistry and liver function tests were essentially normal. Complete blood count and differential showed a hematocrit of 36.8%, platelet count of 228 × 109/L, white blood cell (WBC) count of 12.8 × 109/L with lymphocyte count of 7.4 × 109/L (57.9%), granulocyte count of 4.7 × 109/L (36%), and eosinophils of 2%. Buffy coat examination of peripheral blood showed relative lymphocytosis with some lymphoid cells characterized by large cerebriform and occasionally clefted nuclei and open lacy chromatin pattern, which constitute >18% of lymphoid cells. Peripheral blood film showed normocytic and normochromic erythrocytes. Serological tests for hepatitis B and C and HIV were negative. Histology result of the wedge biopsy for the back tumor showed ulcerated, mildly spongiotic epidermis, with subepithelial bullous formation overlying a dense dermal inflammatory infiltrate composed of predominantly lymphocytes and few histiocytes. Interspersed within these are thick collagen bundles [Figure 3] and [Figure 4]. Immunohistochemical analysis of CD4/CD5/CD8 and CD30 was not done due to limited resources.
|Figure 3: Section showing an ulcerated epidermis overlying dermis with diffuse infiltration by monomorphic population of lymphoid cells (MG ×40)|
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|Figure 4: Section showing diffuse infiltration of superficial dermis by monomorphic population of lymphoid cells (MG ×200)|
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A diagnosis of MF/SS stage IIIB (T4, N1, and M0) was made, and the patient was commenced on cytotoxic chemotherapy using weekly methotrexate, and oral prednisolone and antihistamines were added. She had some improvement following initiation of above therapy. Two months later, she relapsed and finally died from overwhelming sepsis.
| Dicussion|| |
CTCL is a heterogeneous group of non-Hodgkin's lymphomas (NHLs), in which the skin is the primary site of involvement. It is characterized by monoclonal expansion of malignant T-cells and primarily helper T (CD4) cells, with MF and SS accounting for the majority of cases. The etiology of MF/SS remains unknown, but genetic, environmental, and infectious agents have been implicated as possible factors. Human retroviruses have been suggested as possible etiologic agents in CTCL. SS is believed to be part of the spectrum of MF (an erythrodermic variant with circulating tumor cells in the blood), which may arise de novo or from preexisting lesions histopathologically classical of MF. It is one of the rarer causes of GED, with the common causes being psoriasis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, chronic actinic dermatitis, pityriasis rubra pilaris, and drug-related causes. Our patient is a 65-year-old female who fall into the common age range for SS of 60–70 years.
MF usually has an indolent course, with patients often having a long premycotic or premalignant phase with itchy eczematous skin eruptions.
The earliest diagnostic phase of MF is the patch phase, characterized by scaly macules and patches that vary in size, shape, and color and that tend to involve sun-protected sites with associated pruritus. The index case presented with an indolent course of the disease, with a long premycotic phase having recurrent eczematous skin eruptions, which have been ongoing for more than 3 years before the mycotic phase that occurred 13 months after her first presentation at the dermatology clinic. This is in keeping with the natural history of MF as highlighted above. The tumor phase is usually preceded by the onset of dome-shaped, deep red to violaceous nodules emerging in areas of uninvolved skin or in preexisting plaques. The tumors may ulcerate, as seen in our patient, and become secondarily infected. The tumor has a predilection for the body folds and face, where dermal thickening, coalescing plaques, and tumors may result in characteristic “leonine facies.” Generalized exfoliative dermatitis may develop as the initial presenting sign of MF/SS or may accompany plaques and tumors, as seen in the index case.
Sézary syndrome is characterized by the triad of exfoliative dermatitis, lymphadenopathy, and circulating atypical mononuclear cells (Sezary cells). It may be accompanied by keratoderma, vitiligo-like hypopigmented patches, alopecia, ectropion, nail dystrophy, ankle edema, intense pruritus, and cutaneous pain. Our patient had intense long-standing pruritus, recurrent erythroderma, axillary lymphadenopathy, as well as Sezary cells on peripheral blood film. She also had scaling and fissuring of palms and soles, alopecia, ectropion, nail dystrophy, and vitiligo-like hypopigmented patches on the legs, which all characterized MF/SS.
In the above index case, the diagnosis of schizophrenia was made by the psychiatrist first before the diagnosis of MF/SS was made later by the dermatologist. However, going by the history of recurrent pruritus dated back to 3 years, which was thought to be the initial premycotic phase of MF, indicates that the MF predates the onset of the schizophrenia. Both MF/SS and schizophrenic disorders in this patient may negatively affect one another, in that the presence schizophrenia may have contributed to the late diagnosis of MF because the initial chronic pruritus may have been confused with delusion of parasitosis, thus leading to misdiagnosis and delay in early diagnosis of MF. The possibility of a secondary schizophreniform disorder (organic schizophrenia) cannot be entirely ruled out in the index case, because of possible tumor metastasis to the brain. However, this is unlikely because the patient has no other neurological signs and symptoms to suggest intracranial space-occupying lesion resulting from metastatic deposits to the brain. More so, the advanced stage of the disease (MF/SS) occurred much more later after the diagnosis of schizophrenia and it is at this stage that possible metastasis to the brain occurs. Brain neuroimaging in this patient may contribute in ruling out possible metastasis.
The initial baseline investigations for MF are complete blood count and peripheral blood film. The result may be normal or shows atypical large lymphocytes with cerebriform nucleus. When the Sezary cells are >5% of total WBC count or absolute count of these cells is >1000/mm3 and then it is suggestive of SS. In our patient, the total count of WBC was 12.8 × 109/L and characteristic Sezary cells were more than 18% of the total leukocytes, that is, the absolute count of Sezary cells was >1000/mm3. This together with generalized exfoliative dermatitis and lymphadenopathy established the diagnosis of SS in our patient. Skin biopsy is considered as a confirmatory investigation for MF. Punch biopsy specimen can be divided into two, one half for routine histology and the other half for immunophenotyping and/or molecular diagnostic studies. The essential histological criteria for diagnosis are (a) a band-like lymphocytic infiltrate in the superficial papillary dermis, (b) epidermotropism, and (c) atypical cerebriform T-cells in the dermal and epidermal infiltrates. The histology report of our patient showed dense infiltrate of lymphocytes in the dermis with intraepidermal collection of lymphocytes, which was consistent with cutaneous lymphoma. Immunophenotyping of peripheral blood could not be done in this patient due to limited resources.
The available treatment options for MF/SS include topical chemotherapy, phototherapy, systemic chemotherapy, electron beam radiotherapy, photon bean irradiation, retinoids, interferons, immunotherapy, and stem cell transplantation. We treated our patient with methotrexate and prednisolone because she was not stable enough to tolerate combination chemotherapy which could have been the best option for her. She had some improvement on that with resolution of the erythroderma, shrinkage of tumor and improvement of pruritus. She was apparently stable for about 2 months before she died.
MF progresses in a manner similar to other low-grade or indolent NHLs. However, patients with Sézary syndrome have a relatively poor prognosis, with a median survival of 3–4 years. The poor prognostic factors reported include patient age of at least 65 years at presentation, overall clinical stage, and circulating Sezary cell count (at least 5% of total lymphocyte count). Skin infections with Staphylococcus aureus and Pseudomonas aeruginosa leading to bacteremia and sepsis remain the most common causes of death in patients with MF/SS. Our patient had poor prognostic signs of advance age, overall clinical stage, and Sezary cells of more than 18%. She succumbed to overwhelming sepsis. Other factors that may have contributed to poor outcome include the coexisting mental illness, which have contributed to misdiagnosis and delay in early diagnosis of MF. The issue of treatment compliance and irregular clinic visits are common problems in individuals with mental illness that have significantly contributed to the poor outcome in our patient.
| Conclusion|| |
SS remains a rare cause of generalized exfoliative dermatitis. The coexistence of MF/SS with mental illness may negatively affect the outcome, by causing misdiagnosis, delay in presentation, and making a definitive diagnosis. Thus, the need for all patients with skin disorders to first presents to the dermatologist before subsequent referrals to other specialists based on indications. Skin biopsy is advocated on all patients with erythroderma for early detection of CTCL.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]