Pyoderma gangrenosum treated with cyclosporin A and prednisone 
Case report 
PYODERMA GANGRENOSUM ASSOCIATED WITH 
IgA PARAPROTEINEMIA. TREATMENT WITH 
CYCLOSPORIN A AND PREDNISONE 
C. Veller-Fornasa, A. Fadel, S. Peruzzo and A. Peserico 
SUMMARY 
A 58-year-old woman with a 20-year history of recalcitrant pyoderma gangrenosum associated with IgA 
paraproteinemia was treated with cyclosporin A 5 mg/kg/day combined with prednisone 30 mg/day without 
significant amelioration. After raising the dose of cyclosporin A to 10 mg/kg a rapid improvement was 
observed. Subsequently the cyclosporin A and prednisone doses were reduced progressively and a complete 
cure was achieved after 7 months of treatment. Three years later no relapse has occurred on a maintenance 
therapy consisting of 3 mg/kg/day of cyclosporin A and 6 mg/day of prednisone. 
KEY WORDS 
pyoderma gangrenosum, treatment, cyclosporin A, prednisone 
INTRODUCTION 
Pyoderma gangreno sum (PG) is a rare disease of 
unknown etiology and slowly progressive course. It 
is characterized by sterile inflammatory lesions, 
sometimes granulomatous and sometimes pustular 
or ulcerative, which show a tendency to scar at the 
center and to extend centrifugally. The course is 
chronic with alternating exacerbations and remissions, 
and vast ulcerations severa! decimeters in diameter 
may develop over months or years, without apparent 
precipitating factors. In 50 to 75% of cases PG is 
associated with a systemic disease, most often ulcerative 
colitis, Crohn's disease, polyarthritis or a gammophaty. 
Immunologic mechanisms have been shown to be 
acta dermatovenerologica A.P.A. Vol 4, 95, No 1 
involved in the pathogenesis of PG: this explains 
the successful use of cyclosporine A (CsA), which is 
characterized by a patent activity mainly on cell-
mediated immunity but also on antibody-dependent 
immunity and chronic inflammatory reactions. CsA 
in the treatment of PG has been well documented 
(1-3). 
The first case of PG treated with CsA was described 
by Curley et al. in 1985 ( 4 ); many other reports 
have followed (5-7). The literature sometimes describes 
therapeutic successes with low dosages of CsA (3-4 
mg/kg/day (18,9)), while other authors suggest .the 
need for a dose of 7-10 mg/kg/day (10-12), also in 
association with systemic steroids ( 4,6,9,10,13). 
The following description is a case report of PG 
27 
Pyodenna gangrenosum treated with cyclosporin A and prednisone 
associated with IgA paraproteinemia which 
was not amenable to standard therapy, but 
was cured with CsA at dosage of 10 mg/kg/ 
Fig. l. Pyoderma gangrenosum: ulceration on 
the leg 
Fig. 3. Atrophic scar on the leg after treatment 
28 
day in association with prednisolone 30/mg/day. 
CASE REPORT 
A 58-year-old woman presented manifestations of pyoderma 
gangrenosum (PG) at various sites since 1973, with alternate 
phases of remission and recrudescence, for which she was 
hospitalized numerous times. In February 1978 far the 
first tirne an IgA paraproteinemia with type k light chain 
was demonstrated to be associated with the PG. On that 
occasion corticosteroid therapy was instituted, which led 
to a remission of the cutaneous symptoms in 5 months. 
One year later, despite maintenance of corticosteroid 
Fig. 2. Pyoderma gangrenosum: ulceration on the lower 
abdomen 
Fig. 4. Atrophic scar on the abdomen following the treatment 
therapy, the lesions reappeared, and in the same year, in 
addition to the monoclonal lgA anomaly, IgG and IgM 
levels fell and Bence Jones protein was detected in the 
urine. Microscopic examination of bone marrow obtained 
acta dennatovenerologica A.P.A. Vol 4, 95, No 1 
Pyoderma gangrenosum treated with cyclosporin A and prednisone 
by a needle biopsy of the sternal bone demonstrated 
hyperplasia of ali the series, particularly the 
megakaryocytic one, and the presence of numerous 
plasma cells. Bone biopsy of the left iliac crest did 
not confirm the diagnostic suspicion of multiple 
myeloma and suggested a mild reactive medullary 
infiltration. A vast PG ulceration developed 
subsequently at the biopsy site, which proved refractory 
to treatment. 
Until 1981 the cutaneous symptoms alternately 
deteriorated and partially regressed The patient was 
given clofazimine, sulfones, steroids and cycles of 
antimitotic therapy in successive periods. In January 
1991 extensive lesions developed on the patient's 
left leg (photo n.1) and abdomen (photo n.2). In 
view of the failure of the previous treatments CsA 
was administered orally at the dose of 5 mg/kg/day 
in two divided doses combined with prednisone 30 
mg/day. As the clinical picture remained unchanged, 
the dose of CsA was progressively increased up to 
10 mg/kg/day over the subsequent 12 weeks, with a 
marked improvement in the symptomatology. Following 
the increase in cyclosporin blood levels (537 mcg/L) 
the drug dose was reduced to 7.5 mg/kg/day. The 
continuous clinical improvement allowed progressive 
reduction of the CsA and prednisone doses to 4 
mg/kg/day and 18 mg/day, respectively. In August 
1991 the patient was completely cured (Fig. 3,4) 
and IgA paraproteinemia had not developed into 
multiple myeloma. To date (February 1994) no 
clinical relapses have occurred with maintenance 
therapy of CsA 3 mg/kg/day and prednisone 6 mg/ 
day. 
COMMENT 
Immunologic mechanism have been shown to be 
involved in the pathogenesis of PG: this explains 
the successful use of CsA, which is characterized by 
a potent activity mainly on cell-mediated immunity 
but also on antibody-dependent immunity and chronic 
inflammatory reactions (1-3). 
After the first repo rt by Curley et al. in 1985 ( 4) 
numerous cases of relapsing PG resistant to the 
usual therapies have been treated successfully with 
CsA (6,7,10,11). Although the mechanism of action 
of CsA in PG is stili unclear, the drug is known to 
act principally by inhibiting immune-mediated 
inflammatory events (15). It may be speculated that 
this inhibition affects not only specific immunologic 
mechanisms (helper T and cytotoxic T) lymphocyte 
dependent activation of IL-2) but also unspecific 
effector cells such as histiocytes and macrophages. 
In additon, the expansion of suppressor T lymphocytes 
is enhanced. 
The efficacy of CsA in PG thus represents further 
evidence, although indirect, of the involvement of 
immunologic mechanisms in the pathogenesis of this 
disease (9,12). 
Our case of PG is similar to the one described by 
Penmetcha et al. (5) with regard to both the severity 
of the cutaneous lesions and the concomitant 
paraproteinemia IgA with type k light chain. In our 
case, unlike in those reported by other authors 
(8,9,13,15), doses of under 10 mg/kg/day were found 
insufficient to control the cutaneous symptomatology. 
CsA therapy did not cause adverse reactions in our 
patient. 
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Pyodenna gangrenosum treated with cyclosporin A and prednisone 
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AUTHORS' ADDRESSES 
30 
Cleto Veller-Fornasa MD, assoc. professor, Clinica Dermatosifilopatica 
Universita di Padova, Via C. Battisti 206, 351000 Padova, Italia 
Adriano Fadel MD, resident, same address 
Stefania Peruzzo MD, resident, same address 
Andrea Peserico MD, professor and chairman, same address 
acta dennatovenerologica A.P.A. Vol 4, 95, No 1