Successful treatment of Sweet's syndrome with doxycycline
`
`lUC]OSHL D.N.ATUKORALA. A.ABANMI. O.AL KHAMlS AND A.HALHHM*
`J.)t•ponmPms a) lli'ml<ttolag!J mul •PulhalagJJ, R(lftlt1h r\rml'll 1-'rmTs Ha;;plli!l. RiJiildlt. Saudi ttrablt!
`/\''""Pted fnr pnblicatl<m I!\ Nnvt'lnht•r I <J'J l
`
`Summary
`
`Two patients with Sweet's syndronw are desc1ibed, both of whom were treated with doxycycline 200
`mg dally, and responded well to therapy. Doxycycline appellrs to be an effective alternative to
`cortlcostcroh:ls for the trefltment of Sweet's syndrome.
`
`In J 964 Sweet 1 descrlbt,>d eight patients with a condltlon
`he designated 'acute febrile neutrophilic dermatosis'.
`and which has subsequently become known as S\·Veet's
`syndrome. This dlsnrder nlmprises fever. ntmtrophil
`!em:oc~'tosis. and skin lesions with characteristic hlsto-
`log!cal features. 2 ~4
`to systemic
`Sweet's syndrome responds rapidly
`corticosteroids, but relapses frequently (>Ccur. '!'his treat·
`ment may not be Ideal for all patients wl.th Sweet's
`syndrome. and sevend alternative ther~:~pies. Including
`potassium iodide.' dofaztmtne. Indomethacin. 7 mkhi-
`clne and dapsone~ h~1ve been tried .. with limited success.
`\·Ve describe two female patients with Sweet's syn-
`drome who responded to treatment with oral doxycy-
`cline.
`
`Case reports
`Case 1
`A 41-year-old Saudi wmnan presented in April 191:!9
`with erythemtltous. indurated. tender plaques tm the
`foreanns (Fig. 1 ). She was apyrexial. and there was nu
`history nf arthropathy. nr recent resp.lrat.ory or urinary-·
`tract infection. She h1:1d suffered from recurrent attacks
`of similar painful skin lesions, mainly on the dorsa of the
`hunds nnd/or forearms for the previous 4 years. The
`lesions were observed to improve when she received
`treatment for her rosacea with dm..:ycydine. Pulmonary
`tuberculosis was diagnosed in 1980. and treated with
`antituberculous therapy for I H months with a multiple-
`drug regimen. In Febmary 1988. she developed Sl:ro-
`ruJoderma 1nvolvlng the ccrvka:llymph nodes. and was
`a further course of antituberculous therapy. This
`was followed by a persistent tuberculous sinus In the
`ned. which was excised in September I 989.
`A skin biopsy from a fore<1m1 lesion showed a dense
`
`l'vrm~pomlcm·c: Dr R.K.Jushi. Riyudh Anm:d Pun;es Ht>~pilal. 1'.0. Box
`7f!'17. Riyadh Ill ~9. Saudi Aruhia.
`
`51-14
`
`infiltrate principally composed of neutrophili. with
`leucocytodasla, and a ft'w hist.iucytcs. There was no
`evidenL"C of true vasculitis, The epidermis was unre~
`mark.able
`l), A full blood count and routine
`biochemistry were ntlrmat The ESR was 68 rom/h.
`Hepatitis serology. and sernlogtcal tests (or syphilis were
`negative. Sktn-slit smears for ac:Jd-fast bacll!.l and Leish-
`mania bodies were negative. Urine and stool -analyses
`revealed no ahnormallty.
`Bec~luse of the previous response to doxycycline, she
`was treated with doxycycline 100 mg twice dally. There
`was Improvement after 1 week of treatment:, and the
`lesions gradually resolved over the nelrt l weeks; In view
`of her previous history of recurrences, she was given a
`further .3 weeks' treatment at u reduced dose of 100 mg
`dally. Thereafter. she did not develop.any further lesions
`during t1 1 "'-month follow-up period.
`
`Case 2
`A 3 7 -yeaNlld Saudi woman was seen in November
`1 9 8 9, with a
`history of recurrent. painful skin.
`lesions consisting of furunculoid and erythematous
`~1laques. These episodes were frequently associated wltb
`respiratory- or urinary-tract lnfectlnns. but on other
`nccasloos there were no obvious predpitatlng factors.
`Skin lesions appeared prt.•dominantly on her llmbs. With
`a few on the trunk and face. She had bee.n seen In out-
`!>atient departments many times, and was admitted to
`hospltHI on three occasions with widespread skin lesions.
`fever and arthralgia. Pregtmncy exacerbated the skin
`lesions. Histology of a skin biopsy showed changes
`similar to those i.n Case I , which were consistent with
`the diagnosis of Swt.>efs syndrome. IJeucocytosls ranged
`between L~H'l <md l6·HxlOY/I (normal r.mge~ll).
`and the HSI\ between .24 and 45 mm/b.
`~fore attending in November 1989, she had been
`treated at another hospital with prednisolone 40 mg
`daily I(Jr f1 weeks. On reducing the dose of prednisolone
`
`Dr. Reddy's Laboratories, Ltd., et al.
`v.
`Galderma Laboratories, Inc.
`IPR2015-__
`Exhibit 1058
`Exh. 1058
`
`

`
`TRKATMKNT OF SWEET'S SYNDROME WITH DOXYCYCMNK
`
`585
`
`Figure I. Case I. Typical lesion of Sweet's syndrome on ihv left
`forearm.
`
`to 10 mg daily, she developed multiple, indurated.
`ei*ythematous plaques surmounted by flaccid blisters.
`In view of the tendency for her lesions to relapse, and
`because of our previous experience with Case 1. we
`added doxycycline 100 mg twice daily, and were then
`able to wean her off the prednisolone. She be^an to
`improve within 2 weeks, but then stopped all medica-
`tions when she became pregnant. There were recurrent
`exacerbations of her skin lesions during the pregnancy,
`which were helped by topical steroids and oral non-
`steroidal anti-inflammatory agents. We saw her again
`after her child was born in lanuary 1992. and she had
`florid skin lesions. Treatment with doxycycline 100 mg
`twice daily was started, and there was a dramatic
`improvement within 2 weeks. The lesions resolved
`completely, leaving residual hypopigmentation. after 4
`weeks. We continued to treat her with a reduced dose of
`100 mg doxycycline daily for 4 weeks, followed by 50
`mg daily for a further 4 weeks. She has been virtually
`free of skin lesions for the past 4 months on this regimen.
`
`Discussion
`Systemic corticosteroids are still considered to be the
`treatment of choice in Sweet's syndrome.'' although in
`cases of relapsing Sweet's syndrome other anti-inliam-
`matory drugs have been tried, with some success.'""
`Both our patients had relapsing Sweet's syndrome.
`Possible precipitating factors could have been tuberculo-
`
`Figure 2. Photomicrograph of skin biopsy from Case 1. The upper and
`mid-dennis is hcaviiy infiiiraieti by inQammatory cells mixed with
`nuclear dust.
`
`sis in the first patient, and respiratory or urinary
`infections in the second patient. Pregnancy is another
`reported exacerbating factor.'"
`We are not aware of any reports of Sweet's syndrome
`treated with tetracyclines. There is. however, one report
`of minocyclitie as a possible causal agent.'' The success
`of doxycycline therapy in our patients is unlikely to be a
`coincidence. Tetracycline has been found to be effective
`in dermatoses with neutrophilic inKltration. Two of six
`female patients with a variant of pustular psoriasis
`reported by Barlow and Schul/J' responded to treatment
`with tetracycline. A combination of nicotinamide and
`tetracycline has been found to be effective in patients
`with bullous pemphigoid." erythema elevatum diuti-
`num.'^ atid linear IgA bullous dermatosis.' ^ Tetracyc-
`line has been found to suppress leucocyte chemotaxis in
`vitro and in vivo at therapeutic serum concentrations."*
`and patients with inllatnmatory acne vulgaris. who were
`
`Exh. 1058
`
`

`
`586
`
`R.K.JOSHI et al
`
`treated with oral tetracycline 1 g daily, showed signifi-
`cant suppression of both random migration and chemo-
`taxis ot neutrophil polymorphonuciear leucocytes.'"
`The pathogenesis ot" Sweet's syndrome is not fully
`understood, but the frequent association with infections
`suggests that bacterial antigens, or antigen-antibody
`complexes, may play a pathogenic role. Antigens result-
`ing from tissue breakdown in malignancy are thought to
`be pathogenic in some cases."* The association with
`arthritis''' and Sjogren's syndrome.^" and the prompt
`response to corticosteroids suggest that Immune mech-
`anisms are involved.
`The effectiveness of doxycycline in our patients might
`be due to a combination of anti-inflammatory effects, the
`inhibition of neutrophil chemotaxis. and its likely sup-
`pressive effects on the complement-mediated inflamma-
`tory process.
`To our knowledge, this is the first report of the
`successful use of doxycycline in Sweet's syndrome, and
`we suggest that a trial of this anti-inflammatory anti-
`biotic be considered in this condition, using doses of 200
`mg daily.
`
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