Benzaquen, Michael

Borradori, Luca

Feldmeyer, Laurence

Imstepf, Valentina A

Lipsker, Dan

Schlapbach, Christoph

JAAD Case Reports

English

PubMed

Imstepf, Valentina A.

PubMed Central

Localized aseptic neutrophilic dermatoses of the extremities triggered by stasis and tissue damage: Two case reports of an unrecognized condition misdiagnosed as bacterial cellulitis

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CASE REPORTFrom theHospitalogic Dof StrasFunding sIRB approCorresponDermat14Localized aseptic neutrophilic dermatoses ofthe extremities triggered by stasis and tissuedamage: Two case reports of an unrecognizedcondition misdiagnosed as bacterial cellulitisValentina A. Imstepf, MD,a Christoph Schlapbach, MD, PhD,a Michael Benzaquen, MD,aLaurence Feldmeyer, MD, PhD,a Dan Lipsker, MD,b and Luca Borradori, MDaKey words: erysipelas-like rash; localized neutrophilic dermatoses; localized Sweet syndrome; lymphedema.Abbreviation used:ND: neutrophilic dermatosisINTRODUCTIONNeutrophilic dermatoses (NDs) are a group ofautoinflammatory dermatoses characterized by anaberrant accumulation of neutrophil granulocytes inthe skin with potential extracutaneous involvementand systemic inflammatory response.1,2 NDs oftenpresent with overlapping clinical and histopatholog-ical features, which led to the proposal of a simpli-fied classification of NDs, encompassing superficialNDs, NDs en plaques, and deep NDs.1NDs are typically associated with hematologicaldisorders, chronic inflammatory, rheumatological,and gastrointestinal diseases. In addition to a varietyof drugs, NDs may also be triggered or aggravated bytraumas, including surgery.1Here, we describe 2 unusual cases of localizedNDs affecting the extremities, in which either acuteor chronic peripheral edema resulted in a misleadinginflammatory reaction that was invariably mistakenas cutaneous infection.CASE REPORTSCase 1A 61-year-old man was referred to the emergencydepartment for a systemic inflammatory syndrome.His past medical history was notable for untreatedmultiple sclerosis and chronic kidney insufficiency.Clinical examination revealed a pronounced edem-atous inflammation of the peripheral extremities(hands, fingers and feet) without any blisters orpustules (Fig 1, A).Department of Dermatology, Inselspital, Bern Universityl, University of Bern, Bern, Switzerlanda; and Dermato-epartment, University Hospitals of Strasbourg, Universitybourg, Strasbourg, France.bources: None.val status: Not applicable.dence to: Valentina A. Imstepf, MD, Department ofology, Inselspital, Bern University Hospital, University ofLight microscopy studies of a skin biopsy spec-imen from the dorsal hand showed a diffuse andperivascular neutrophilic infiltrate, with leucocyto-clasia and extravasation of erythrocytes in the entireedematous dermis with no evidence of vasculitis(Fig 2).Laboratory tests showed an elevated C-reactiveprotein level up to 204 mg/L (normal, \5 mg/L)and an increased white blood cell count of 36 G/L(normal, 3-10.5 G/L) with 89% neutrophilicgranulocytes.Blood and urine cultures, polymerase chain reac-tion test for SARS-CoV-2, and microbiological cultureof skin biopsy specimens remained negative. A severehypoalbuminemia of 10 g/L (normal, 35-52 g/L) withmicroalbuminuria was explained by severe malnutri-tion and renal dysfunction.The patient was treated with protein-rich nutrition,clobetasol proprionate cream and an empiricallyintravenous co-amoxicillin therapy for 5 days, allow-ing quick regression of the inflammatory syndromeand peripheral edema (Fig 1, B).Case 2A 47-year-old woman presented with an acutepainful left red leg and fever (temperature up toBern, Freiburgstrasse 34, 3011 Bern, Switzerland. E-mail:valentina.imstepf@insel.ch.JAAD Case Reports 2022;28:14-7.2352-5126 2022 by the American Academy of Dermatology, Inc. Publishedby Elsevier, Inc. This is an open access article under the CC BYlicense (http://creativecommons.org/licenses/by/4.0/).https://doi.org/10.1016/j.jdcr.2022.07.036Fig 1. A, Symmetric acral involvement with an acute painful erythematous swelling of thedorsal surface of hands and fingers. B, Quick regression of the inflammatory syndrome andperipheral edema 5 days after treatment with topical clobetasol proprionate cream, empiricalintravenous antibiotics, and protein-rich nutrition.Fig 2. A, B, Light microscopy studies of a skin biopsy specimen obtained from the dorsalsurface of the hand showing a diffuse and perivascular neutrophilic infiltrate, withleucocytoclasia and extravasation of erythrocytes in the entire edematous dermis with noevidence of vasculitis (A and B, Hematoxylin-eosin stain; original magnifications: A, 3100; B,3200.)JAAD CASE REPORTSVOLUME 28Imstepf et al 1540 8C). She experienced at least 5 similar episodesduring the previous year. The latter were unsuccess-fully treated as bacterial cellulitis with differentantibiotics, although pathogens could not be de-tected in the blood cultures. The patient sufferedfrom chronic venous insufficiency because of mul-tiple deep venous thromboses due to a factor VLeiden mutation, for which she was treated withacenocoumarol. On examination, she had an edem-atous, erythematous, warm, and painful left leg. SheFig 3. A, Painful swelling and redness in the left leg, warm and tender to touch, mimicking anerysipelas or a cellulitis associated with systemic symptoms and fever (temperature up to40 8C). Erythematous papules and plaques with pseudobullous appearance on the left forearm(Inset). B, Complete regression of the clinical signs and the inflammatory syndrome aftertreatment with oral prednisolone. Signs of chronic venous stasis with varicose veins andpigmentation can be recognized.Fig 4. A, B, Light microscopy studies of a skin biopsy specimen obtained from the left legdemonstrating a strong dermal edema with superficial and deep neutrophil-rich infiltrate(A and B, Hematoxylin-eosin stain; original magnifications: A, 3100; B, 3200.)JAAD CASE REPORTSOCTOBER 202216 Imstepf et alalso showed erythematous papules and plaques witha pseudobullous appearance on the left forearm andabdomen (Fig 3).Light microscopy studies of a skin biopsy spec-imen from the left leg showed strong dermal edemawith a superficial and deep neutrophil-rich infiltrate(Fig 4).Direct immunofluorescence microscopy studiesremained negative. A computed tomography scan ofthe left leg showed no evidence of an underlyingnecrotizing fasciitis. A duplex sonography scanrevealed no sign of deep venous thrombosis.Laboratory tests found a C-reactive protein levelup to 173 mg/L and neutrophilia of 20.5 G/L. Bloodcultures remained negative. An extensive work-updid not find any evidence for either an extracuta-neous organ involvement or an associated systemicdisease, including a hematological malignancy.JAAD CASE REPORTSVOLUME 28Imstepf et al 17The patient was treated with intravenous methyl-prednisolone 250mg/d for 4 days, and then with oralprednisolone (0.75 mg/kg/d), with progressivetapering over 2 weeks. This regimen resulted in thecomplete regression of all cutaneous signs andthe systemic inflammatory syndrome (Fig 3, B).The patient was then given colchicine 1.5 mg/d and, in the following year, she only had 2 mildepisodes of red leg, which were controlled by a shortcourse of oral prednisolone.DISCUSSIONOur 2 observations represent striking inflamma-tory dermatosis associated with an inflammatorysystemic response that closely mimicked acutebacterial infections. Although in 1 case, the acuteeruption affected acral edematous areas, the secondcase was characterized by acute relapsing episodesinvolving an edematous leg related to chronicvenous insufficiency. Although a search for under-lying infectious pathogens remained negative inboth cases and antibiotics showed little effect onthe clinical course, both patients had an inflamma-tory dermatosis with histologically dermal edemawith a neutrophil-rich infiltrate, which promptlyresponded to topical/systemic corticosteroids andanti-inflammatory drugs, such as colchicine.Hence, these 2 cases should best be considered asautoinflammatory reactions triggered by a distur-bance of the local homeostasis. We have recentlydescribed a series of patients with erythematous,inflammatory papules, plaques, and extensive infil-trated lesions, histologically characterized by adermal neutrophil-rich inflammatory infiltrate thataffected sites of surgery, chronic venous insuffi-ciency, or lymphedema. Identical clinical pheno-types have previously been reported under a varietyof confusing names.3-7Therefore, we have proposed the unifying term of‘‘localized NDs triggered by tissue injury’’ to betterdescribe similar conditions that pose diagnostic andclassification challenges.5 In our second case, thedevelopment of cutaneous lesions at distance fromthe primarily affected site suggests, that these local-ized NDs potentially spread under certaincircumstances.This question is clinically and economically rele-vant because of the significant incidence of erysip-elas and bacterial cellulitis in the Westerncountries.8,9 The idea that some of these cases areincorrectly diagnosed as bacterial cellulitis and ratherrepresent a localized ND is supported by 3 observa-tions. First, some cases of these ‘‘infectious’’ derma-toses respond to simple anti-inflammatory regimensalone.8 Second, despite antibiotic prophylactic treat-ment, relapses surprisingly occur in more than 40%of patients. Finally, acute pseudocellulitis is a well-recognized condition that is frequently misdiag-nosed and unnecessarily treated with antibiotics inthe inpatient setting. Pseudocellulitis has beenrelated in up to 30% of cases to venous stasis and isalmost invariably mechanically explained by venoushypertension.9 Therefore, it is conceivable that both,rapid and chronic abnormal interstitial fluid andtranscapillary fluid imbalance, result in tissue dam-age and local ischemia, leading to activation ofdamage-associated molecular pattern moleculeswith an inflammatory reaction,5 with cytokinesactivating neutrophilic leukocytes.10 In this setting,the presence of bacterial antigens, such as lipopoly-saccharides, might also contribute to theinflammation.2Better knowledge of these reactive, noninfectiousdisorders, which fulfill the criteria for an autoin-flammatory disorder, is important to improve diag-nostic accuracy and decrease hospital admissionsand unnecessary antibiotic use.Conflicts of interestNone disclosed.REFERENCES1. Wallach D. Neutrophilic dermatoses: an overview. Clin Derma-tol. 2000;18(3):229-231.2. Marzano AV, Ortega-Loayza AG, Heath M, Morse D,Genovese G, Cugno M. Mechanisms of inflammation inneutrophil-mediated skin diseases. Front Immunol. 2019;10:1059.3. Demitsu T, Tadaki T. Atypical neutrophilic dermatosis on theupper extremity affected by postmastectomy lymphedema:report of 2 cases. Dermatologica. 1991;183(3):230-233.4. Petit T, Frances C, Marinho E, Herson S, Chosidow O. Lym-phoedema-area-restricted Sweet syndrome during G-CSFtreatment. Lancet. 1996;347(9002):690.5. Gloor AD, Feldmeyer L, Rammlmair A, Schlapbach C, Wallach D,Borradori L. A relapsing localized variant of neutrophilicdermatosis triggered by tissue injury. Br J Dermatol. 2021;184(1):162-164.6. Gutierrez-Paredes E, Gonzalez-Rodrıguez A, Molina-Gallardo I,Jorda-Cuevas E. Neutrophilic dermatosis on postmastectomylymphedema. Actas Dermosifiliogr. 2012;103(7):649-651.7. Park JY, Kang HY, Kim YC. Neutrophilic dermatosis confined tothe lymphedematous area. Ann Dermatol. 2014;26(3):411-413.8. Raju S, Tackett P Jr, Neglen P. Spontaneous onset of bacterialcellulitis in lower limbs with chronic obstructive venousdisease. Eur J Vasc Endovasc Surg. 2008;36(5):606-610.9. Strazzula L, Cotliar J, Fox LP, et al. Inpatient dermatologyconsultation aids diagnosis of cellulitis among hospitalizedpatients: a multi-institutional analysis. J Am Acad Dermatol.2015;73(1):70-75.10. Ruocco E, Puca RV, Brunetti G, Schwartz RA, Ruocco V.Lymphedematous areas: privileged sites for tumors, infections,and immune disorders. Int J Dermatol. 2007;46(6):662.

Localized aseptic neutrophilic dermatoses of the extremities triggered by stasis and tissue damage: Two case reports of an unrecognized condition misdiagnosed as bacterial cellulitis.

Valentina A. Imstepf

Christoph Schlapbach

Michael Benzaquen

Laurence Feldmeyer

Dan Lipsker

Luca Borradori

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Localized aseptic neutrophilic dermatoses of the extremities triggered by stasis and tissue damage: Two case reports of an unrecognized condition misdiagnosed as bacterial cellulitis.

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