Departments of Haematology and Dermatology, Royal Infirmary of Edinburgh
SummaryPyoderma gangrenosum at the site of sternal marrowaspirate was observed in a patient with acute myelo-proliferative disease characterized by a high peripheralblood basophilia. Lesions with a similar appearancewere also seen on the palate. No other disease knownto be associated with pyoderma gangrenosum could bedemonstrated. A review of the literature suggests thatmyeloproliferative disease should now be recognized asoccurring in association with pyoderma gangrenosum.
IntroductionPyoderma gangrenosum is a rare skin disorder
which typically takes the form of one or moreplaques, each with an area of central necrosisdelineated by a characteristic bluish-red border.Although most commonly reported (Domonkos,1971) in association with ulcerative colitis andrheumatoid arthritis, pyoderma gangrenosum hasalso been noted in other clinical syndromes includingacute and chronic myeloproliferative disease (Perryand Winkelmann, 1972; Shore, 1976; Cramers,1976). The authors now describe a patient withan acute myeloproliferative disorder characterized bya pronounced and persistent peripheral blood baso-philia and the occurrence of pyoderma gangrenosuminitiated by sternal marrow puncture.
Case reportA previously healthy 53-year-old salesman gave a
12-month history of malaise, weight-loss, nightsweats and recurrent respiratory tract infections.There was a family history of diabetes mellitus,his mother being a late-onset, insulin-dependentdiabetic. Initial clinical examination revealedgeneralized pallor, hepatomegaly of 5 cm and aspleen just palpable at the costal margin.The initial haemoglobin concentration was 10-1
g/dl, with a platelet count of 64 x 109/1, a white cellcount of 12-4 x 109/1 (differential: 19% neutrophils,20% lymphocytes, 10% monocytes, 19% eosino-phils, 22% basophils, 4% myelocytes, 4%/ promyelo-cytes and 2° blast cells), a reticulocyte count of
6-5%, erythrocyte sedimentation rate of 15 mm/hourand additionally two nucleated red cells per 100white cells were noted. The blood film showed baso-philic stippling, neutrophil toxic granulation andpseudo-Pelgerization. The leucocyte alkaline phos-phatase score was 19 (normal range 20-100).Sternal marrow aspirate, obtained with difficulty,showed megaloblastic erythropoiesis, an increase inpromyelocytes and blast cells, numerous bizarrebasophils, basophil precursors and ringed sidero-blasts. Iliac crest trephine biopsy demonstratedhypercellularity with a prominence of blast cellsand excess reticulin. The serum B12 was greater than1000 ng/l (normal range 170-7000 ng/l) and theserum folate and Schilling test were normal.
Stools were repeatedly strongly positive to testingfor faecal occult blood, but barium studies of thegastrointestinal tract were normal and no abnor-mality of haemostasis other than thrombocytopeniacould be demonstrated. There was no evidence ofhaemolysis in that the direct and indirect anti-globulin tests were negative, there was no urinaryhaemosiderin, and the plasma haemoglobin, serummethaemalbumin and plasma haptoglobin werewithin normal limits.
Initial treatment was blood transfusion. Inaddition, in view of his symptoms and the presenceof a strongly positive Mantoux test, a diagnosis ofoccult tuberculosis was considered and a trial ofethambutol and isoniazid begun. Although nightsweats and malaise diminished, bacteriologicalconfirmation of tuberculosis was never obtaineddespite culture of urine, sputum and marrow.On follow-up, utilizing standard surgical tech-
niques and thiomersal as a topical antiseptic, arepeat sternal marrow aspiration was attempted butwas a dry tap. One week later a large, painful, redswelling developed in the skin at the site ofaspiration. This lesion developed central necrosisand when the necrotic area was removed the ulcerhad a cribriform base with a ragged bluish-redoverhanging edge characteristic of pyodermagangrenosum. This lesion slowly extended in size to
FIG. 1. This illustrates the initial lesion of pyoderma gangrenosum over the sternum, and lowerleft is the second lesion at early stage of development.
reach a diameter of 5 cm. Later a second painfulswelling, identical in appearance to the first,developed near the first lesion (Fig. 1). Biopsy ofthis second area showed an infiltrate of lymphocyticcells in the epidermis and around the dermal bloodvessels, while bacteriological studies revealedStaphylococcus aureus but no anaerobic organisms.The pyoderma gangrenosum responded rapidly to60 mg prednisolone/day, but mild diabetes mellitus,controlled well by diet and chlorpropamide, deve-loped.On further investigation at this time the following
results were negative or within the normal range:urea and electrolytes, liver function tests, calcium,phosphate, uric acid, serum proteins, protein electro-phoresis, immunoglobulins, cryoglobulins, serumviscosity, anti-nuclear factor, LE cell preparation,rheumatoid arthritis latex test, ASO titre, VDRLflocculation test, TPHA test, prothrombin timeratio, PTTK, fibrinogen, fibrin degradation productsethanol gelation test, prothrombin consumptionindex, serum lysozyme, neutrophil function tests,skin antibody immunofluorescence tests and CH50and C4 levels, while the C3 level was slightlyelevated at 2-74 g/l (normal range 0 85-2 54 g/l).The patient appeared to improve subjectively on
the treatment previously outlined with an increase inhis sense of well-being and reduction in night
sweats. His steroid dosage was gradually reduced to10 mg/day, but he then developed two necrotic areasin the palate closely resembling the pyodermagangrenosum present on his chest (Fig. 2). Nosignificant bacterial infection could be demonstratedin these lesions.He became more anaemic, requiring further blood
transfusions which eventually totalled 34 units in the4 months after presentation, and severely thrombo-cytopenic (platelet count 12 x 109/l), resulting inpurpura and recurrent epistaxes. His total whiteblood count remained within normal limits, but thebasophil count fluctuated markedly, reaching morethan 40°% of the total white cell count on severaloccasions. Myeloid precursors were invariablypresent in the peripheral blood count, but the blastcell count never exceeded 5°/.A trial of oxymetholone produced no clinical
improvement or reduction in transfusion require-ment, and eventually the patient died 4 monthsfollowing his initial presentation. A post-mortemfailed to reveal any known association of pyodermagangrenosum. The marrow showed intense erythroidhyperplasia, normoblastic in type and negative toperiodic acid-Schiff staining, with reduction in allother cell lines. Whilst no firm diagnosis could bereached the overall appearances were considered tobe consistent with erythroleukaemia.
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FIG. 2. This illustrates two large ulcerated areas on palate resembling pyoderma gangrenosum.
DiscussionPyoderma gangrenosum has been reported in
association with ulcerative colitis, rheumatoidarthritis, regional ileitis, dermatitis herpetiformis,hypogammaglobulinaemia, paraproteinaemia andmyeloma (Domonkos, 1971). Other associationsinclude active chronic hepatitis (Byrne, Hewitt andSummerly, 1976), immunosuppression (Haim et al.,1973) and disseminated intravascular coagulation(Staughton and Copeman, 1976). Alterations ofcellular immunity have also been noted (Shore, 1976).Pyoderma gangrenosum has occurred in a case ofacute lymphoblastic leukaemia maintained inremission by prednisolone, methotrexate and 6-mercaptopurine, whilst non-specific leukaemia hasoccurred following 6-mercaptopurine, for pre-existing pyoderma gangrenosum (Shore, 1976).There have been a number of reports in the
literature of this rare skin condition occurring inassociation with myeloproliferative diseases, in-cluding acute myeloblastic leukaemia, myelofibrosis,chronic myeloid leukaemia, polycythaemia rubravera and acute myelomonocytic leukaemia (Perryand Winkelmann, 1972; Shore, 1976; Cramers, 1976).Few of these reports, however, were fully docu-mented and the authors were fortunate in being ableto investigate their patient extensively. Nevertheless,no definitive haematological diagnosis was possiblebut the initial marrow findings together with theabnormal peripheral blood, the rapid progression ofthe disease and the post-mortem findings suggest
that the disorder could be classified within themyeloproliferative spectrum as defined by Gunz andBaikie (1974), and was acute in type. A peculiarfeature was the persistent peripheral blood baso-philia. Whether the pyoderma gangrenosum and thebasophilia were causally related is open to specu-lation.
Finally, accepting the fact that there is no satis-factory means of causally linking the skin lesions andthe underlying haematological disorder, the natureof the pyoderma gangrenosum in this case wasunusual in two respects. The primary lesion deve-loped on the site of a recent sternal marrow puncturesuggesting that direct trauma by some unknownmeans precipitated the epidermal necrosis. Secondly,the patient had lesions resembling pyodermagangrenosum on the palate, a site of involvementwhich has rarely, if ever, been implicated.
AcknowledgmentsWe wish to thank Dr S. H. Davies for permission to
report his patient, Dr S. Urbaniak of the Blood TransfusionService for undertaking the neutrophil function studies andcomplement levels, Dr H. White and Dr J. D. McGregor ofthe Pathology Department of the University of Edinburgh,and Miss J. Donnelly for typing the manuscript.
ReferencesBYRNE, J.P.H., HEWITT, M. & SUMMERLY, R. (1976) Pyo-derma gangrenosum associated with active chronichepatitis. Archives of Dermatology, 112, 1297.
CRAMERS, M. (1976) Bullous pyoderma gangrenosum inassociation with myeloid leukaemia. Acta dermato-venereologica, 56, 31 1.
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DOMONKOS, A.N. (1971) Andrews'Diseases ofthe Skin, p. 926.W. B. Saunders, Philadelphia.
GUNZ, F. & BAIKIE, A. (1974) Leukemia, 3rd edn. Grune &Stratton, New York.
HAIM, S., FRIEDMAN-BIRBAUM, R., BETTER, O.S. & TUMA, S.(1973) Skin complications in immunosuppressed patients;follow-up of kidney recipients. British Journal of Derma-tology, 89, 169.
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