Toxic epidermal necrolysis-like presentation of paraneoplastic pemphigus due to underlying thymoma: A clinical conundrumK Poonia1, K Chabra1, U Dalal2, M Bhalla1
1 Department of Dermatology, Government Medical College and Hospital, Chandigarh, India
2 Department of Surgery, Government Medical College and Hospital, Chandigarh, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.JPGM_752_20
Source of Support: None, Conflict of Interest: None
A 35-year-old female presented with multiple painful oral ulcers and cutaneous eruptions for 7 days. Oral ulcers were associated with severe pain, difficulty in swallowing, and excessive salivation. On day 3 of illness, she noted multiple fluid filled flaccid blisters with underlying painful erythema which ruptured spontaneously and peeled off in sheets leaving behind eroded areas and hemorrhagic crusting [Figure 1]a, [Figure 1]b, [Figure 1]c. Extremities also had target lesions with central necrosis resembling erythema multiforme. She reported taking an analgesic (paracetamol) for unrelated condition before onset of lesions. Initially, clinical possibility of toxic epidermal necrolysis (TEN) was considered and supportive measures such as withdrawal of analgesic, maintenance of fluid and electrolytes, and paraffin gauge dressing. Patient was started on oral methylprednisolone (16 mg). But, there was no improvement and lesions were progressive. She underwent skin biopsy which revealed suprabasal bulla with few apoptotic keratinocytes [Figure 2]a. Acantholytic cells were seen on Tzanck smear. Nikolsky sign and bulla spread sign were positive. Direct immunofluorescence showed IgG fluorescence in intercellular space of the keratinocyte cell surfaces and C3 deposition in the basement membrane zone [Figure 2]b and [Figure 2]c. Chest X-ray film showed mediastinal widening. Computed tomography of chest showed a large well defined heterogeneously enhancing mass (of 4.5 cm) in prevascular and left paravascular region, medially extending between left common carotid artery and subclavian artery causing splaying, also abutting trachea medially and abutting arch of segment [Figure 1]d, consistent with thymoma. Based on these findings, she was diagnosed as paraneoplastic pemphigus (PNP) associated with thymoma. She was initiated on oral cyclophosphamide (50 mg once daily) and dose of oral methylprednisolone increased to 48 mg. After 3 weeks of diagnosis of underlying tumor, thymectomy was performed when patient was on 36 mg of methylprednisolone. The tumor was an encapsulated mass measuring 7 × 5.8 × 4 cm. Histopathology showed sheets of interspersed population of lymphocytes and epithelial (tumor) cells without invasion into surrounding tissues, consistent with thymoma, type B2 [Figure 1]e and [Figure 1]f. Oral cyclophosphamide was stopped after 2 months and steroids tapered over 6 months with complete resolution of skin lesions with post-inflammatory hyperpigmentation [Figure 1]g and [Figure 1]h. At 18 months of follow-up, patient is doing well and with no recurrence of symptoms.
Several mechanisms have been proposed by which an underlying neoplasm induces autoimmunity that include: antitumor immune response cross-reacting with the normal epithelial proteins such as desmoglein and plakins, desmocollins inducing autoimmunity by molecular mimicry, or by epitope spreading. PNP has been described in association with both malignant as well as benign tumors.
The acute presentation of symptoms along with a history of drug intake prior to the onset of lesions led to an initial clinical diagnosis of TEN. However, clinical progression of symptoms despite drug withdrawal and supportive measures prompted us for further work-up. Clinically it may be difficult to differentiate TEN from PNP as mucocutaneous lesions with hemorrhagic crusting and erythema multiforme-like lesions may be common to both entities. Histopathological features are also overlapping. Histopathological changes are variable in PNP and includes intraepidermal acantholysis, keratinocyte necrosis, and vacuolar interface dermatitis. Direct immunofluorescence shows deposition of IgG and complement in epidermal intercellular spaces and granular linear complement deposition along epidermal basement membrane zone.,
Long-term morbidity and mortality in patients with PNP depends upon multiple factors that includes underlying malignancy, immunosuppressive therapy, and infection- associated complications. In contrast to patients with malignant tumor-associated PNP, cases associated with benign tumors, such as benign thymomas and localized Castleman's disease show better prognosis when tumor is removed.
Presentation of thymoma is usually asymptomatic. About half of these patients may have associated other autoimmune diseases such as myasthenia gravis, pure red cell aplasia, systemic lupus erythematosus, and Goodpasture syndrome. Several cutaneous disorders described in association with thymoma includes pemphigus vulgris, bullous pemphigoid, lichen planus, vitiligo, alopecia areata, and lupus erythematosus. However, TEN-like presentation of PNP is not commonly reported in association with thymoma. After an extensive literature search, only 10 cases of Steven Johnson syndrome/TEN-like presentation of PNP were found, most of the cases were reported in association with chronic lymphocytic leukemia.,,, Kokubu et al. reported TEN mimicking PNP in patient of follicular lymphoma. To best of our knowledge, TEN-like presentation of PNP in association with benign thymoma has never been reported.
To conclude, the present case highlights the importance of ruling out alternative diagnosis in patients with suspected TEN, with PNP being a close differential diagnosis as treatment and long term outcome is entirely different for both entities.
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[Figure 1], [Figure 2]