pyoderma gangrenosum with leukaemoid reaction dhillon et al...

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INTRODUCTIONPyoderma gangrenosum (PG) is an uncommon,ulcerative cutaneous condition of uncertainaetiology.1 It is associated with systemicdiseases in at least 50% of patients who areaffected.2 The diagnosis is made by excludingother causes of similar-appearing cutaneousulcerations, including infection, malignancy,vasculitis, collagen vascular diseases, diabetesand trauma. In a process termed pathergy, newulcerations may occur after trauma or injury tothe skin in 30% of patients who already havepyoderma gangrenosum.2

The classic ulcerative form of PG usuallyobserved on the legs, and a superficial variant(atypical PG) tends to occur on the hands.Patients with PG may have involvement ofother organ systems that manifests as sterile

neutrophilic infiltrates. Culture-negativepulmonary infiltrates are the most commonextracutaneous manifestation.2 Other organssystems that may be involved include the heart,the central nervous system, the gastrointestinal(GI) tract, the eyes,the liver, the spleen, thebones, the lymph nodes and the breast.Although breast cancer would be the mostlikely differential clinical diagnosis in anypatient with breast ulceration, other rare causesshould be considered. We report the case of ayoung lady who presented with bilateral breastulcerations due to PG.

CASE REPORT

A 26-year-old lady presented with painfululcers on both breasts of 3 months duration.The first manifestation of ulcers first becameapparent following consumption of oral

Case Report:Pyoderma gangrenosum breast with leukaemoid reaction:

a rare clinical entityK.S. Dhillon,1 Alisha Khan,1 J. Fatima,2 P. Shukla,3 K.R. Varshney4

Departments of 1Dermatology, 2Medicine, 3Pathology, 4Microbiology, Eras Lucknow Medical College & Hospital,Lucknow

ABSTRACTBreast ulceration is an alarming sign for clinicians and it places a significant physical and psychological burden on thepatient. We report the rare presentation of Pyoderma gangrenosum (PG) of the breast with secondary leukaemoidreaction. A 26-year-old lady was referred to us from medicine department for evaluation of recurrent ulcers involvingboth breasts for the last three months. Physical examination revealed symmetrical bilateral ulcers on both breasts;nipples were spared. The total leucocyte count was high (40,800/mm3). Patient was thoroughly investigated to rule outany associated systemic disorder. Based on the clinical presentation and haematological picture a diagnosis of PGwith leukaemoid reaction was made. Patient was treated with systemic steroids, clofazimine and topicalimmunomodulators. After 6 weeks of treatment, the ulcers resolved significantly and her leucocyte count becamenormal. The patient is on regular follow-up and is doing well.

Key words: Pyoderma gangrenosum,Breast, Leukaemoid reactionDhillon KS, Khan A, Fatima J, Shukla P, Varshney KR. Pyoderma gangrenosum breast with leukaemoid reaction: a rareclinical entity. J Clin Sci Res 2014;3:46-50.

Received: 29 May, 2013.

Corresponding author:Dr K.S. Dhillon, Professor, Department ofDermatology, Eras Lucknow Medical College &Hospital, Lucknow, Uttar Pradesh, India.e-mail: [email protected]

Pyoderma gangrenosum with leukaemoid reaction Dhillon et al

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medication prescribed by a local practitionerfor fever. The ulcer started as a small boil withyellow discharge and then increased in size ata rapid pace. Right breast was affected firstfollowed by left. The ulcer healed after afortnight to some extent. Subsequently, theulcers recurred on both breasts for which shewas treated with topical as well as systemicmedications by a local practitioner. The presentepisode was the third recurrence. She had nohistory of recent gastrointestinal upset, arthritisor other systemic symptoms. The patient hadnot previously undergone any surgicalintervention nor a biopsy from the ulcer site.However, she had received 4 units bloodtransfusion for severe anaemia before reportingto us.

Clinical examination revealed two ulcers,located in the upper medial quadrant of bothbreasts, measuring approximately 7 × 10 cm(right breast) and 3 × 5 cm (left breast) in size.The necrotic ulcers had violaceous underminedborder which were rapidly advancing. Theulcers were very tender. Nipples were notinvolved (Figure1). Oral examination showederosion in both retromolar pillars. Abdominalexamination was unremarkable. Laboratoryevaluation revealed haemoglobin 9.7 g/dL witha normal mean corpuscular volume (90.4 fL);elevated total leucocyte count (40,800 / mm3);the platelet count was 2.25 lakh/ mm3. In theperipheral blood smear erythrocytes werenormocytic and normochromic, neutrophilswere markedly increased and platelets wereadequate in number. No abnormal cells orhaemoparasites were seen. The erythrocytesedimentation rate (ESR) was elevated (26 mmat the end of the first hour). Screening for autoantibodies was negative. The culture andsensitivity testing of the ulcer swab showed thegrowth of Enterococcus faecalis. Urine cultureshowed the growth of Klebsiella oxytoca.Serum biochemistry was normal.

Ultrasonography and mammography of bothbreasts were normal.

Punch biopsy taken early in the disease andfrom the advancing, erythematous bordershowed an infiltrate of chronic inflammatorycells confined to the dermis (Figure 2). Featuressuggestive of vasculitis were evident at the edgeof the ulcer, with a perivascular lymphocyticinfiltrate and fibrinoid necrosis of the dermalvessel wall. Occasionally, extravasation of redblood cells and areas of thrombosis was alsoseen. Ulceration of the epidermis secondary todermal inflammation was present (Figure 2).

The patient was treated with oral prednisolone50 mg daily and clofazimine 400 mg daily alongwith topical corticosteroids (0.1% betametha-sone cream) and topical tacrolimus 0.03% forthe first 4 weeks; systemic steroids were taperedoff and stopped. Symptomatic treatment wasadministered for fever and anaemia. With thistreatment, the patient’s condition significantlyimproved (Figures 3 and 4). After 6 weeks oftreatment, the ESR was 18mm at the end ofthe first hour and the TLC became normal(9000/mm3). Peripheral blood smear showeddecrease in neutrophil counts while otherfindings remained as before, after 6 weeks oftreatment. She has been counselled to come forregular follow-up visits and is still continuingoral clofazimine along with topical immuno-modulators.

Figure 1: Clinical photograph showing necrotic ulcers withviolaceous undermined borders which were rapidlyadvancing in the upper medial quadrant both breasts


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DISCUSSION

The incidence of PG is uncertain, but it isestimated to be 3-10 patients per millionpopulation per year.1 PF can occur can at anyage but is seen most commonly between 20 and50 years of age;1

The aetiology of PG is unknown and thepathogenesis is poorly understood. Althoughthe disease is idiopathic in 25%-50% ofpatients, an underlying immunologic abnor-mality may exist as suggested by its frequentassociation with systemic diseases like infla-

mmatory bowel disease (IBD), pulmonary,cardiac, autoimmune disorders; and neo-plasia.1-3

Occurrence of the phenomenon of pathergy,(i.e., the development of new lesions oraggravation of existing ones following trivialtrauma) frequently observed in PG wouldsuggest altered, exaggerated, and uncontrolledinflammatory responses to non-specificstimuli.1

The term leukaemoid reaction describes anelevated white blood cell count, or leucocyto-sis, that is a physiological response to stress orinfection. Leukaemoid reactions are generallybenign and constitute a response to a significantdisease state. Haemorrhage, drugs, infections,asplenia and diabetic ketoacidosis are thecommon causes of leukemoid reaction.

Immune status dysregulation particularlyneutrophil dysfunction (i.e., defects inchemotaxis or hyperreactivity) in individualswith PG has been suggested. Evidence ofabnormal neutrophil trafficking and metabolicoscillations have also been described in PG.These two factors would have resulted in thedevelopment of leukaemoid reaction.

Figure 2: Photomicrograph showing lymphocyticinfiltrate within the dermis suggestive of vasculitis atthe edge of the ulcer, with a perivascular lymphocyticinfiltrate and fibrinoid necrosis of the dermal vessel wall(Haematoxylin and eosin, × 1000)

Figure 3: Clincal photograph of right breast obtainedafter 6 weeks of treatment with oral prednisolone, topicaltacrolimus and clofazimine

Figure 4: Clincal photograph obtained after 6 weeksshowing healed lesions in the left breast


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Diseases commonly associated with PG includeinflammatory bowel disease, ulcerative colitis,Crohn’s disease. Haematologic disorders com-monly associated with PG include leukaemiaor preleukaemic states (predominantly myelo-cytic) and monoclonal gammopathies, prima-rily of immunoglobulin A variety.4-6

Reported therapies for PG have often focussedon treatment of the underlying condition.Therefore, most information available relatesto systemic therapies, probably because manyPG lesions mimic the activity of the underlyingdisease.7

First-line therapy includes immuno-suppres-sants, such as corticosteroids (prednisolone/methylprednisolone) and cyclosporin.8 Othertherapeutic options include immuno-modulators, biologicals and antileprosy drugs.When an underlying disease is absent, as in ourpatient PG can respond variably to standardtherapy. Further, PG can even recur afterdefinitive surgery for the underlying disease,(e.g., colectomy).9

A case of PG of the sinus mammarum has beendocumented in a patient with ulcerative colitis.9

In this case the cutaneous ulcer was resistantto conventional systemic medical therapyalthough the treatment resulted in improvementin the systemic disease. Basing on thehistopathologic finding of vasculitis at the edgeof the lesions antithrombotic topical injectionswere used as an adjunct to standard treatment.9

This case report suggested that perilesionalinjections of calcic heparin were successful ininducing remission.9

A retrospective analysis (n=20) showed thattopical steroids have little role in healing.3

Conversely, other authors have demonstratedimprovement of the lesions with intralesionalsteroids.14

Surgery has to be used with caution since itcan trigger PG . Any surgical procedure has to

be done as an adjunct to immunosuppressiononly in patients with stable disease or partialremission. Autologous split-skin grafts havebeen used with variable outcome.10 Asignificant disadvantage of split-skin grafts isthe necessity to create a new wound at the donorsite. Therefore, surgical intervention is notrecommended in standard practice.

In comparison with the previous cases of PGwith pathergy complicating coronary arterybypass grafting (CABG),11-12 our patient’s caseseemed to be unusually severe, as evidencedby the leukaemoid reaction. Two cases ofpostoperat ive PG that presented withleukaemoid reaction, have been reported.13

Till date 43 cases of PG of the breast have beenreported.1 In 30 of the cases PG lesions weresecondary to trauma to the breast tissue, suchas surgical intervention, reconstruction of thebreast, biopsy, and intramuscular injection.1 Itis likely that, the pathergy phenomenon maybe the reason for PG lesions occuring afterbreast trauma.

Our patient had a rare presentation of PG ofthe breast with leukaemoid reaction, in whichpresently, there are no signs of underlyingmalignancy. This case highlights theimportance of considering PG as one of thedifferential diagnoses of breast ulcers. Carefulspecialist clinical assessment could establishan early diagnosis and formulate an effectivemanagement plan. Our knowledge aboutpathogenesis and individual risk factors for thedevelopment of PG is still rather limited. Thishampers the efforts for prevention. However,the appearance of new ulcers can be preventedin patients known to have the disorder byavoiding excessive trauma to the skin.

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Pyoderma (ecthyma) gangrenosum: Clinical andexperimental observations in five cases occurringin adults. Arch Dermatol Syph 1930; 22:655-80.


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2. Bolognia JL, Jorizzo JL, Julie VS. Dermatology.Chapter 26. London, UK: Mosby;2003.p.1:423-8.

3. Hasselmann DO, Bens G, Tilgen W, Reichrath J.Pyoderma gangrenosum: clinical presentation andoutcome in 18 cases and review of the literature. JDtsch Dermatol Ges 2007;5:560-4.

4. Freedberg IM, Fitzpatrick TB, Eisen AZ, GoldsmithLA, Austen KF, Wolff K. Pyoderma Gangrenosum.Fitzpatrick’s dermatology in general medicine,5th Edition. New York: McGraw-Hill,1999;2:2207-13.

5. SuWP, Davis MD, Weenig RH, Powell FC, PerryHO. Pyoderma gangrenosum: clinicopathologiccorrelation and proposed diagnostic criteria. Int JDermatol 2004;43:790-800.

6. Branagan NM, Higgins SP, Halim SA, Le TH.Systemic polyarteritis nodosa mimicking pyodermagangrenosum in a rare association with smalllymphocytic leukaemia/chronic lymphocyticleukaemia. Clin Exp Dermatol 2009;34:127-9.

7. Johnson WT, Norva WM. Cutaneousmanifestations of inflammatory bowel disease. In:Lukash WM, Johnson RB, editors. The systemicmanifestations of inflammatory bowel disease.Springfield: Charles C. Thomas; 1975.p.212.

8. Tromm A, May D, Almus E, Voigt E, Greving I,Schwegler U, et al. Cutaneous manifestations ininflammatory bowel disease. Z Gastroenterol2001;39:137-44.

9. Angiò LG, Pirrone G, Rivoli G, Fracassi MG, RosatoA, Piazzese E, et al. Pyoderma gangrenosum ofthe “sinus mammarum” in ulcerative colitis. G Chir2003;24:247-54.

10. Rozen SM, Nahabedian MY, Manson PN.Management strategies for pyoderma gangrenosum: case studies and review of literature Ann PlastSurg 2001;47:310-5.

11. Rand RP, Olerud JE, Verrier ED. Pyodermagangrenosum after coronary artery bypass graftingAnn Thorac Surg 1993;55:1016-8.

12. Koss-Harnes D, Ovrum E, Langeland T. Pyodermagangrenosum as a complication of coronary arterybypass grafting. Eur J Cardiothorac Surg1995;9:163-5.

13. Ryu J, Naik H, Yang FC, Winterfield L. Pyodermagangreno sum presenting with leukemoidreaction: a report of 2 cases. Arch Dermatol2010;146:568-9.

14. Jennings JL. Succesful treatment with Intralesionalsteroids. J Am Acad Dermatol 1983;9:575-80.


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