A Case Report of Chronic Lymphocytic Leukemia With ...

KMJ Vol. 6 No. 3 (July-September) 2012
A Case Report of Chronic Lymphocytic Leukemia
With Paraneoplastic Pemphigus
Javid Rasool*, Sajad Jeelani**, Afaq***, Shazia Handoo****, S Imran*****
45 years female presented in October 2003 with
bilateral axillary lymph nodes, 4 nodes on either side,
biggest node in right axilla measuring approximately
4x5cms while on the left side the biggest node was
measuring approximately 8x7 cms. Rest of her physical
examination was unremarkable. Investigations revealed Hb
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13.0 gms/dl, TLC 48.85 and a platelet count of 135/mm .
DLC revealed P4, L95 and Mono 1. Patient was diagnosed
as chronic lymphocytic leukemia (CLL)-Binet A (RAI stage
I). Her CD 38 was negative and karyotype revealed
hypoploidy (50% metaphases showed 45 chromosomes).
th
She was put on follow-up till March 30 , 2004 when CBC
revealed Hb 13.5, TLC 151.74, DLC P2, L88, PL10 and
platelet 098. Patient was started on tab. Cyclophosphamide
50 mg bid and predicort 40 mg OD. Three months later
patient developed vesiculobullous lesions on legs (Fig 1 and
2) and was shifted to chlorambucil plus prednisolone. On
th
March 8 , 2005 CBC of the patient showed Hb 14.7, TLC
6.33, DLC P34, L63, E3 and platelet count of 091. Patient
however, continued to have on and off these skin lesions
with minimal mucosal lesions as well. The lymph node size
was regressing on either side and was measuring
approximately 3x3 cms. In 2006, patient was asymptomatic
and continued with vesicular lesions. Skin biopsy
histopathological Sections revealed presence of lining
squamous epithelium having spongiosis and small blister
formation. In the subdermal area lot of inflammatory cells
are seen. Features favor diagnosis of pemphigus.
*Assistant Professor, ** Consultant Clinical, ***Sr. Resident Clinical Haemotology SKIMS, ****Tutor Demonstrator Deptt Pathology GMCS
KMJ 2012; 6(3):990-992
Multiple Blisters on Left Leg One Vesiculobullous Lesion on Same Leg
Srinagar, ***** Lecturer Deptt Physiology GMC Srinagar.
Address for correspondence: JAVID RASOOL E-mail: dr_javidrasool@yahoo.co.uk
Kashmir Medical Journal
C a s e R e p o r t
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KMJ Vol. 6 No. 3 (July-September) 2012
Skin Biopsy Showing Subepidermal Cleft Suggestive of
Paraneoplatic Pemphigus
Immunofluoresence showed no fluorescence seen with anti
Ig G, Ig A, Ig M, C3 and fibrinogen. CBC at the time of skin
biopsy was revealing Hb 13.3, TLC 9.31, DLC N14, L81, E5
and platelet count of 124. Patient at this point of time was
on endoxan and predicort as she could not continue
chlorambucil due to financial constraints.
Patient was treated for pemphigus by adding
sulfasalazine (sazo) 1tab bid, Dapsone 50mg bid, QYN 200
mg BT, predicort was increased from 40 to 60 mg daily dose
and cyclophosphamide was continued as per schedule. No
treatment related complication has been noticed till date.
Currently patient is asymptomatic with physical
revealing mild pallor, static nodes (~3x3 cms) no bullous
lesions.
The latest CBC available on reveals as Hb 9.6,
TLC 5.49, DLC N6.9, L90.9. Mono 1.8 and a platelet count
1
of 098. Anhalt and coworkers suggested that the term
paraneoplastic pemphigus, which is clinically distinct from
pemphigus vulgaris and pemphigus foliaceus, be applied to
the painful, persistent and treatment resistant erosions of
the oral mucosa, vermilion borders of the lips and
conjunctiva that appear in patients with various types of
cancers, including chronic lymphocytic leukemia (CLL).
These acantholytic mucocutaneous lesions are
characterized by auto antibodies that are pathogenic after
passive transfer.
Cutaneous lesions occur in up to 25% of patients
with CLL. These can be caused either by cutaneous seeding
Kashmir Medical Journal
by leukemic cells (leukemic cutis, LC) and other malignant
diseases or non malignant disorders. Skin infiltration with Blymphocytic
CLL manifests as solitary, grouped or
generalized papules, plaques, nodules or large tumors.
Prognosis in CLL patients with LC is rather good and many
authors claim that it does not significantly affect patient's
survival. However, prognosis is poor in patients in whom
LC shows blastic transformation (Richter's syndrome) and
when the leukemic infiltrations in the skin appear after the
diagnosis of CLL. Secondary cutaneous changes seen in
CLL are of infectious or hemorrhagic origin. Other
secondary lesions present as vasculitis, purpura, generalized
pruritis, exfoliative erythroderma and paraneoplatic
pemphigus (PP). An exaggerated reaction to an insect bite
2
and an insect bite like reaction have also been observed.
Oppenheim (1910) probably reported the first
patient with CLL and a pemphigoid like skin disease,
although the 2 patients reported by Sachs (1921) had a more
certain diagnosis of CLL. A clear antibody proven bullous
pemphigoid in association with CLL was not achieved until
1974 when [Cuni et al] described a single case.
Patients with PP develop characteristic Ig G auto
antibodies against several antigens including membranes of
the plakin family, bullous pemphigoid antigen I and
desmosomal proteins. Ig A pemphigus is another recently
characterized immunobollous disease that presents as a
vesiculopustular eruption with neutrophilic infiltration and
epidermal acantholysis. Mucus membrane involvement is
3
rare.
These patients have auto antibodies that bind to a
distinct complex of epidermal proteins, including
desmoplakin I (250 KD), major bullous pemphigoid antigen
(230kD), desmoplakin II (210kD) and 190-kD and a 170
KD protein, neither of which has been further
characterized. Histological findings include acantholysis,
epidermal cell necrosis, vacuolar interface changes and
sometimes, lichenoid infiltrates of the upper dermis. Direct
immunofluouresence shows an intracellular deposition of
immnnoreactants in the epidermis and granular deposition
at the dermal-epidermal deposition junction. Indirect
immunoflouresecence with rodent bladder as a substrate
shows an intercellular pattern. This method is the most
convenient and cost effective method of screening for PP,
since antigens of both pemphigus vulgaris and pemphigus
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KMJ Vol. 6 No. 3 (July-September) 2012
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foliaceus are not expressed in this tissue.
Numerous autoantibodies can be detected
serologically in CLL patients but only infrequently correlate
with clinical disease. In a study by GIMEMA group 41% of
CLL patients had at least one positive marker of
autoimmunity e: g. antinuclear antibody (ANA) or
rheumatoid factor (RF), and 30 out of 194 cases (16%) of
autoimmune diseases in CLL patients were non-
5
hematological. These were mostly observed in stage A
patients in contrast to hematological autoimmunity, which
was much more common in advanced (stage B and C)
disease. However, age matched controls have a similar
prevalence and distribution of serological and clinical
autoimmunity, and these may therefore be coincidental
findings. Some of the autoimmune conditions described in
the literature, such as paraneoplatic pemphigus and
glomerulonephritis (due to antineutrophil cytoplasmic
References
1) Anhalt GJ, Kim SC, Stanley JR, et al: Paraneoplastic
Pemphigus: An autoimmune mucocutaneous disease
associated with neoplasia. N Eng J Med 323: 1729, 1990.
2) Robak E, Robak T. skin lesions in chronic lymphocytic
leukemia. Leuk lymphoma. 2007 May; 48(855-65).
3) Taintor AR, Leiferman KM, Hashimoto T, Ishii N,
Zone JJ, Hull CM: A noval case of IgA paraneoplastic
pemphigus associated with chronic lymphocytic
leukemia. J Am Acad Dermatol. 2007 May 56; (5 suppl);
S73-6.
4) Zillikens D, Brocker EB: paraneoplastic pemphigus.
Induction of auto antibodies against structural protein
Kashmir Medical Journal
antibody) have been triggered by fludrabine and may
therefore be a true complication rather than a chance
association. These may be fatal. Angioedema although rare
seems to be caused by a product of the CLL and is also seen
in other lymphoid malignancies.
A patient with CLL who developed PP soon after
the initiation of fludrabine therapy has been reported.
Several agents had been initiated to bring the disease under
control originally, but a partial remission was achieved and
maintained with mycophenolate mofetil and low dose
6
prednisolone.
Treatment with alemtuzumab(anti CD52)severe
cases of PP in CLL has been recommended when a 68 year
old male with four years history of B-CLL presented with a
wide spread blistering eruption on the extremities and trunk
7
and a severe stomatitis.
in the skin (article in Germany). Hantarzt. 1994 Dec;
45(12): 827-33.
5) Barcellini W, Capalbo S, Agostinelli RM, et al.
Relationship between autoimmune phenomena and
disease stage and therapy in B-cell chronic lymphocytic
leukemia. Haematologica. 2006; 91: 1689-1692.
6) Powell AM, Albert S, Oyama N, Sakuma-OyamaY,
Bhogal B, Black MM. J Eur Acad Dermatol Venereol
May; 18(3): 360-4 Abstract quote.
7) Howy , Bang K, Steiniche T, Peterslund NA, d' Amore F.
Eur J haematol. 2004 Sep; 73(3): 206-9 Abstract quote.
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