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DERMATOLOGICA SINICA 35 (2017) 34e36

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Dermatologica Sinica

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CASE REPORT

A rheumatoid arthritis patient with chronic recurrent annularneutrophilic dermatosis: Are we dealing with a new type ofrheumatoid arthritis-associated dermatosis?

Ece Nur Degirmentepe 1, *, Emek Kocatürk 1, Tulin Yuksel 1, Pırıl Etikan Akbas 1,Ilteris Oguz Topal 1, Nesimi Büyükbabani 2

1 Department of Dermatology and Venereology, Okmeydanı Training and Research Hospital, Istanbul, Turkey2 Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

a r t i c l e i n f o

Article history:Received: Jan 27, 2016Revised: May 11, 2016Accepted: Jun 13, 2016

Keywords:annularneutrophilicrecurrentrheumatoid arthritis

Conflicts of interest: The authors declare that they hnon-financial conflicts of interest related to the subjediscussed in this article.* Corresponding author. Okmeydanı Training and R

Street No. 27, Sisli, 34384 _Istanbul, Turkey.E-mail address: ecenuryksel@gmail.com (E.N. Deg

http://dx.doi.org/10.1016/j.dsi.2016.06.0021027-8117/Copyright © 2016, Taiwanese Dermatologiccreativecommons.org/licenses/by-nc-nd/4.0/).

a b s t r a c t

Neutrophilic dermatoses comprise a heterogeneous group of disorders, which are characterized by in-flammatory skin lesions that share a common histopathological feature, intense inflammatory infiltrationconsisting primarily of neutrophils, with no evidence of vasculitis. We describe a 75-year-old man withrheumatoid arthritis, who presented with erythematous edematous plaques. The histopathologicalfindings indicated neutrophilic dermatosis; however, the patient was afebrile and without an elevatedwhite blood cell count or systemic involvement. We think that the most suitable expression for thisvariant with clinical manifestations different from those of classical Sweet syndrome is “chronic recur-rent annular neutrophilic dermatosis,” as introduced by Christensen et al.1

Copyright © 2016, Taiwanese Dermatological Association.Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://

creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

The term “chronic recurrent annular neutrophilic dermatosis(CRAND)”was first used by Christensen et al1 in 1989 to refer to theskin lesions of two patients who had chronically recurring out-breaks of generalized annular erythematous, edematous cutaneousplaques with histopathological findings suggestive of Sweet syn-drome, but without fever or systemic signs and symptoms.

Case Report

We describe a 75-year-old man with a 10-year history of rheuma-toid arthritis (RA) who presented to our clinic with recurrent out-breaks of edematous, infiltrated, annular, erythematous plaqueswith a violaceous center. The lesions first appeared ~3 years beforeadmission, were located on the patient’s trunk, arms, legs, neck,

ave no financial orct matter or materials

esearch Hospital, Darulaceze

irmentepe).

al Association. Published by Elsevi

and scalp (Figures 1Ae1C), and lasted for 3 weeks. The familyhistory was negative for similar conditions. Upon admission, thepatient was afebrile, and did not have malaise, myalgia, orlymphadenopathy. He had been taking nonsteroidal anti-inflammatory drugs for RA for 10 years. A complete blood countrevealed anemia of chronic disease, and the results of routinebiochemical testing were normal. His C-reactive protein level was81 mg/L (reference range, 0e5 mg/L) and erythrocyte sedimenta-tion rate was 71 mm/h (reference range, <20 mm/h). Chest radi-ography revealed sequelae of tuberculosis in both pulmonaryapices. Abdominal ultrasound showed a solid intravesical bladdermass. The histopathological findings of a biopsy of the mass wereconsistent with papillomatous hyperplasia. Serological testing forevidence of infection with hepatotropic viruses, human immuno-deficiency virus, and syphilis was negative. No other serologicaltesting was performed. The patient was negative for the tumormarkers prostate-specific antigen, carcinoembryonic antigen, andcancer antigen-19.9, and his stool was negative for occult blood.Serum immunoelectropheresis findings were also normal. Togetherwith the patient’s physical examination and history, the clinicalassessment was negative for an underlying malignancy, and noadditional investigations for the presence of an underlying malig-nant tumor were performed.

er Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://

Figure 1 (A) Erythematous, edematous, annular plaques with violaceous centerlocated on the trunk; (B) annular erythematous, edematous lesions located on theupper trunk and neck; (C) reddish-violaceous annular lesions on the arms.

Figure 2 (A) Edema and intense neutrophilic inflammatory infiltrate in the dermis(hematoxylineeosin �200); (B) perivascular neutrophil predominant dense infiltrateand leucocytoclasia (hematoxylineeosin �400).

E.N. Degirmentepe et al. / Dermatologica Sinica 35 (2017) 34e36 35

A skin biopsy specimen showed neutrophilic infiltrate in theupper and mid-dermis, as well as leukocytoclasis. No vasculitis wasobserved (Figures 2A and 2B). Colchicine and dapsone, whichinhibit neutrophil chemotaxis, were used to treat the infiltrate.However, because of the patient’s low hemoglobin level and theoccurrence of diarrhea, they were discontinued. The lesions wereattributed to poorly controlled RA, and the patient was referred to arheumatologist, who prescribedmethylprednisolone (10mg/d) andmethotrexate (10 mg/wk) for 2 months. The lesions gradually dis-appeared. However, the patient stopped taking the methylpred-nisolone and methotrexate because he was worried about the side

effects. Two weeks after the treatment was stopped, the lesionsreappeared. At a 6-month follow-up visit, the patient complainedof severe arthralgia and widespread lesions involving his entirebody. He again refused systemic treatment with methylpredniso-lone and methotrexate.

Discussion

In 1989, Christensen et al1 reported two patients with chronicallyrecurring outbreaks of generalized annular erythematous, edema-tous plaques. The histopathological findings were consistent withSweet syndrome; however, the patients presented without fever orother findings characteristic of Sweet syndrome. Christensen et al1

regarded these two cases as a unique entity because of the annularlesions and the absence of systemic manifestations, and used thedescriptive term “chronic recurrent annular neutrophilic derma-tosis” for the condition, instead of considering it to be a variant ofSweet syndrome.

Romero Aguilera et al2 reported four cases that manifested asafebrile recurrent outbreaks occurring over a course of severalyears. The clinical appearance and histopathological features of theskin lesions of all four patients were suggestive of Sweet syndrome,but none of the patients at any time developed leukocytosis or

E.N. Degirmentepe et al. / Dermatologica Sinica 35 (2017) 34e3636

neutrophilia. However, these authors considered this presentationto be a variant of Sweet syndrome and not a separate entity.

Cabanillas et al3 reported a patient with a 6-month history ofgeneralized painful annular erythematous, edematous plaques. Thepatient did not present with fever or leukocytosis, but did haveneutrophilia and an elevated erythrocyte sedimentation rate. Thelesions improved after a course of oral prednisone, and the patientonly had occasional mild recurrences. The authors considered theircase to resemble more closely Christensen et al’s1 CRAND instead ofbeing a variant of Sweet syndrome.

Koguchi et al4 described a case of figurate erythema that washistopathologically characterized by neutrophilic infiltration. It wassuccessfully treated with potassium iodide. The authors thoughtthat their case could be considered to be a variant of CRAND.

In 2014, Mir-Bonaf�e et al5 reported a novel case of CRANDassociated with RA, as in our patient. They obtained a successfuloutcome using dapsone plus colchine to prevent additional re-currences over a 2-year follow-up period.

CRAND is a very rare condition; to the best of our knowledge,only five cases have been reported to date. Since no association hasbeen found with drugs, infections, or systemic illness, its etiologyremains unknown.5 It is clinically characterized by recurrent out-breaks of indurated annular plaques with erythematous bordersand a violaceous center. Fever, generalized symptoms such asmalaise and myalgia, leukocytosis, and neutrophilia are absent. Thehistopathological findings include neutrophilic infiltration in themid and upper dermis, leukocytoclasia, and no signs of vasculitis.4,5

The one case of RA-associated CRAND reported by Mir-Bonaf�eet al5 did not appear to manifest flare ups of CRAND linked to ex-acerbations of RA.We initially thought that the exacerbations of thelesions of our patient were associated with poorly controlled RA,and the rheumatologist who saw the patient prescribed systemicmethotrexate and methylprednisolone. The lesions disappeared 2weeks after the start of treatment and reappeared after the cessa-tion of treatment. We observed that the appearance of the lesionswas associated with worsening arthralgia.

RA skin manifestations can be either specific or nonspecific. Thespecific manifestations include subcutaneous nodules (classicalrheumatoid nodules, accelerated rheumatoid nodules, or rheuma-toid nodulosis), rheumatoid vasculitis, granulomatous dermatitides(interstitial granulomatous dermatitis or palisaded neutrophilicgranulomatous dermatitis), and neutrophilic dermatosis (pyo-derma gangrenosum, Sweet syndrome, rheumatoid neutrophilicdermatitis, neutrophilic dermatitis of the dorsal hands, pyogenicsterile arthritis, pyoderma gangrenosum, acne syndrome/synovitis,acne, pustolosis, hyperostosis, osteomyelitis syndrome).6

RA-associated neutrophilic dermatosis has been linked to mu-tations in the genes regulating innate immunity, which can induceinflammasome-mediated neutrophil recruitment.7,8 Sweet syn-drome is rarely seen in patients with RA, and is characterized his-topathologically by a neutrophilic infiltrate in the superficial derma

and clinically by the sudden onset of fever, an elevated white bloodcell count, and erythematous, tender skin lesions.9 Rheumatoidneutrophilic dermatosis presents with papules, erythematous pla-ques, nodules, and urticarial lesions with typical symmetric dis-tributions on the joints, extensor surfaces of the extremities, andthe trunk. Histopathological findings include neutrophilic infiltratein the dermis without vasculitis.

The lesions of our patient most closely resembled those of pa-tients with Sweet syndrome, except for the recurrent and annularnature of the lesions and absence of constitutional signs andsymptoms such as fever and myalgia. We included rheumatoidneutrophilic dermatosis in the differential diagnosis, but our pa-tient’s lesions were edematous plaques instead of polymorphiclesions or pustules, andwere distributedwidely instead of confinedto the joints or extensor surfaces of the extremities.10

In conclusion, we described a rare case of a patient with RAwhodeveloped a neutrophilic dermatosis with an atypical, chronic, andrecurrent presentation. We think that “CRAND,” a descriptive termfirst used by Christensen et al,1 to be the most appropriate name forthis dermatological manifestation accompanied by clinical findingsdifferent from those of classic Sweet syndrome. We suggest thatthis is a new entity of RA-associated neutrophilic dermatosis, pre-senting as recurring lesions that worsen with the exacerbation ofRA.

Additional studies of large series of similar cases can help usclarify whether or not CRAND is a new type of RA-associatedneutrophilic dermatosis.

References

1. Christensen OB, Holst R, Svensson A. Chronic recurrent neutrophilic derma-tosis. An entity? Acta Derm Venereol 1989;69:415e8.

2. Romero Aguilera G, Lopez Estebaranz JL, de Pablo P, et al. Chronic recurrentafebrile neutrophilic dermatosis. Actas Dermosifilogr 1994;85:305e8.

3. Cabanillas M, Suarez-Amor O, Sanchez-Aguilar D, et al. Chronic recurrentneutrophilic dermatosis: a possible variant in the spectrum of neutrophilicdermatoses. Actas Dermosifiliogr 2008;99:61e3.

4. Koguchi H, Arita K, Yamane N, et al. Erythema annulare centrifugum-likeneutrophilic dermatosis: effects of potassium iodide. Acta Derm Venereol2012;92:333e4.

5. Mir-Bonaf�e JM, Santos-Dur�an JC, Santos-Briz A, et al. Chronic recurrent annularneutrophilic dermatosis associated with rheumatoid arthritis. Actas Dermosi-filiogr 2014;105:953e5.

6. Marzano AV. Cutaneous manifestations in rheumatoid arthritis. Clin Dermatol2013;1:53e9.

7. Marzano AV, Menicanti C, Crosti C, et al. Neutrophilic dermatoses and in-flammatory bowel diseases. G Ital Dermatol Venereol 2013;148:185e96.

8. Marzano AV, Cugno M, Trevisan V, et al. Role of inflammatory cells, cytokinesand matrix metalloproteinases in neutrophil-mediated skin diseases. Clin ExpImmunol 2010;162:100e7.

9. Rosmaninho A, Carvalho S, Lobo I. Neutrophilic dermatoses revisited. Eur Med JDermatol 2014;2:77e85.

10. Brown TS, Fearneyhough PK, Burruss JB, et al. Rheumatoid neutrophilicdermatitis in a woman with seronegative rheumatoid arthritis. J Am AcadDermatol 2001;45:596e600.