Fig 1. Catastrophic antiphospholipid syndrome. A, Ten-der, reticulated, hyperpigmented plaques on bilateralthighs. B, Progression to hemorrhagic bullae. C, Punchbiopsy from thigh shows diffuse microthrombi in papillaryand reticular dermis.

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Adam Asarch, MD,a Brian L. Swick, MD,a,b andJanet A. Fairley, MDa,b

Department of Dermatology, University of IowaHospitals and Clinics,a and Department of Vet-erans Affairs,b Iowa City, Iowa

Supported by a Merit Review award from theDepartment of Veterans Affairs, Veterans HealthAdministration (Dr Fairley).

Conflicts of interest: None declared.

Correspondence to: Adam Asarch, MD, Departmentof Dermatology, University of Iowa Hospital andClinics, 200 Hawkins Dr, Iowa City, IA 52242

E-mail: adam-asarch@uiowa.edu

REFERENCES

1. Houghton JP, Ianosi-Irmie M, Trooskin SB, Michael H. An

unusual presentation of pemphigus vulgaris. Gastroenterol

Hepatol 2008;4:68-70.

2. Rao PN, Samarth A, Aurangabadkhar SJ, Pratap B, Lakshmi TS.

Study of upper gastrointestinal tract involvement in pemphigus

by esophago-gastro-duodenoscopy. Indian J Dermatol Vene-

reol Leprol 2006;72:421-4.

3. Su O, Onsun N, Meric Teker A, Cinkaya A, Yasemin Korkut A,

Seremet S, et al. Upper airway tract and upper gastrointestinal

tract involvement in patients with pemphigus vulgaris. Eur J

Dermatol 2010;20:792-6.

4. Kanbay M, Selcuk H, Gur G, Yilmaz U, Boyacioglu S. Involvement

of the esophagus in a patient with pemphigus vulgaris who

was on immunosuppressive therapy. J Natl Med Assoc

2006;98:1369-70.

http://dx.doi.org/10.1016/j.jaad.2012.03.003

Catastrophic antiphospholipid syndrome

To the Editor: A 37-year-old African Americanwoman was admitted to the hospital with weaknessand pain in her abdomen and thighs. Her medicalhistory was significant for severe eclampsia andmultiple thrombotic events, which resulted in end-stage renal disease and a diagnosis of antiphospho-lipid syndrome (APS). The diagnosis of APS wasconfirmed with positive serology on two occasionsseparated by several months, and led to the initiationof lifelong anticoagulation therapy with warfarin.The patient was known to be noncompliant withanticoagulation, but had a therapeutic internationalnormalized ratio at the time of her hospital admis-sion. Within 1 week during hospitalization, thepatient developed livedo reticularis (Fig 1, A) andhemorrhagic bullae on her thighs (Fig 1, B) andbreast with severe hypotension, encephalopathy,respiratory failure, and thrombocytopenia. Multipleantibiotics were implemented for a presumptivediagnosis of sepsis, however all cultures were neg-ative. A medium vessel vasculitis and calciphylaxis

were considered, however punch biopsy specimensof skin lesions showed an extensive thrombogenicvasculopathy (Fig 1, C ) with no inflammatory infil-trate or calcium deposition. Multiple causes withconsistent histopathologic findings were considered,including warfarin-induced skin necrosis, heparin-induced thrombocytopenia and thrombosis, purpurafulminans, APS, type I cryoglobulinemia, cryofibrin-ogenemia, and various hereditary thrombophilicdisorders, prompting a full hypercoagulabilityworkup. Antiplatelet factor 4, cryoglobulin, cryofi-brinogen, factor V Leiden, protein S, and theantiphospholipid antibodies were all within normallimits. Despite negative laboratory findings, a

Table I. Catastrophic antiphospholipid syndromeregistry characteristics1

Female 72%Mean age, y 37Primary APS 46%Develop CAPS de novo 46%History of systemic lupuserythematosus

40%

First clinical manifestation(CAPS)

Pulmonary (24%), neurologic(18%), renal (18%)

Pulmonary complications 63.9% (Acute respiratorydistress, pulmonaryemboli)

Cerebral complications(most common causeof death)

62% (Seizures, encephalopathy,stroke)

Skin complications 50.2% (Livedo reticularis,purpura, necrosis)

Cardiac complications 51% (Valve defects,myocardial infarction)

Thrombocytopenia 46%

Adapted from analyses performed on 280 reported cases.

APS, Antiphospholipid syndrome; CAPS, catastrophic antiphos-

pholipid syndrome.

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presumptive diagnosis of catastrophic APS (CAPS)was made and intravenous immunoglobulin, plas-mapheresis, corticosteroids, and aggressive antico-agulation with intravenous heparin were started.Repeated laboratory tests revealed an elevated lupusanticoagulant and anti-beta-2-glycoprotein IgA anti-bodies, supporting the diagnosis and treatment plan.Despite initial stabilization, the patient’s conditiondeclined and she subsequently died. Autopsy re-vealed pulmonary emboli, a splenic infarct, ischemicbowel secondary to diffuse thrombi, and no evi-dence of calciphylaxis. These findings, in addition tothe positive antiphospholipid serologies, confirmeda definitive diagnosis of CAPS. This case has subse-quently been reviewed and accepted into the inter-national CAPS registry.

CAPS, or Asherson syndrome, is a rapidly pro-gressive condition found in 1% of patients with APS.Precipitating events are identified in 53% of cases,and include infection, surgery, medications, andinconsistent anticoagulation.1,2

To definitively diagnose this condition, patientsmust demonstrate evidence of involvement of 3 ormore organs, systems, and/or tissues; have develop-ment of manifestations simultaneously or in less than1 week; have histopathologic confirmation of smallvessel occlusion in at least one organ or tissue; andhave laboratory confirmation of the presence ofantiphospholipid antibodies, which include lupusanticoagulant, anticardiolipin antibodies, and/oranti-beta-2 glycoprotein antibodies.2

Prompt diagnosis is crucial, but can be challeng-ing for several reasons. The condition is rare, andmay not be considered in patients without history ofAPS. Even if considered, patients may fail to meet fulldiagnostic criteria secondary to false-negative anti-phospholipid antibody values in the acute setting, areported occurrence in the literature.3 To furthercomplicate the picture, patients with CAPS maypresent similarly to patients with septicemia byfulfilling systemic inflammatory response syndromecriteria. The cause of this phenomenon is unknown,however evidence suggests it may be the result ofwidespread cytokine release from affected necrotictissues or via molecular mimicry of antiphospholipidantibodies with infectious antigens in the body.4

Early treatment is imperative, and consists ofintravenous immunoglobulin, plasmapheresis, ste-roids, and anticoagulation. Other reported therapiesinclude cyclophosphamide, rituximab, prostacyclin,and fibrinolytics. Even with treatment, prognosis ispoor with a 30% mortality.1,5

An international CAPS registry was created in 2000to analyze the 280 reported cases. Patient data canbe accessed online at http://www.med.ub.es/

MIMMUN/FORUM/CAPS.HTM (Table I). Cutaneousmanifestations were observed in 50% of reportedpatients,1 highlighting an important opportunity fordermatologic consultants to recognize this uncom-mon condition.

Leilani R. Townsend, DO,a Jenny P. Cotton, MD,PhD,b David A. Altman, MD,a and Stuart R.Gildenberg, MDa

Dermatologya and Dermatopathology,b St JosephMercy Hospital, Ypsilanti, Michigan

Presented orally at the Michigan DermatologicalSociety Meeting, Ypsilanti, Michigan, March 23,2011.

Funding sources: None.

Conflicts of interest: None declared.

Correspondence to: Leilani Townsend, DO, Derma-tology, St Joseph Mercy Hospital, 5333 McAuleyDr, Suite 5003, Ypsilanti, MI 48106.

E-mail: Leilani37@yahoo.com

REFERENCES

1. Cervera R. Update on the diagnosis, treatment, and prognosis

of the catastrophic antiphospholipid syndrome. Curr Rheuma-

tol Rep 2010;12:70-6.

2. Cervera R. Catastrophic antiphospholipid syndrome (CAPS):

update from the ‘CAPS Registry.’ Lupus 2010;19:412-8.

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3. Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid

syndrome: updated diagnostic algorithms. Autoimmun Rev

2010;10:74-9.

4. Espinosa G, Cervera R, Asherson RA. Catastrophic antiphospho-

lipid syndrome and sepsis. A common link? J Rheumatol

2007;34:923-6.

5. Espinosa G, Bucciarelli S, Asherson RA, Cervera R. Morbidity and

mortality in the catastrophic antiphospholipid syndrome: path-

ophysiology, causes of death, and prognostic factors. Semin

Thromb Hemost 2008;34:290-4.

http://dx.doi.org/10.1016/j.jaad.2012.03.010

Fig 1. Reticular erythematous patches on upper aspect ofback.

Fig 2. Mid-dermal elastolysis. Interstitial histiocytic in-flammation and multinucleated giant cells with elasticfiber phagocytosis. (Hematoxylin-eosin stain; originalmagnification: 3200.)

Erythematous reticular patches: A rarepresentation of mid-dermal elastolysis

To the Editor: Mid-dermal elastolysis (MDE) is a rareentity consisting of mid-dermal elastic tissue loss.MDE typically presents clinically with fine wrinkling(type I) or perifollicular papular protrusions (type II)on sun-exposed areas, such as the trunk and upperextremities, of Caucasian females.1-3 We present twocases of MDE presenting as persistent reticular ery-thema, a less common clinical variant with suggestednomenclature of type III MDE.1

Patient 1 is a 71-year-old nonsmoking man withdiabetes mellitus, hypertension, hyperlipidemia, onchronic hemodialysis who presented with a large,reticulated, erythematous, blanchable patch on theupper aspect of his back (Fig 1). The duration wasunknown and the lesions were asymptomatic. Theclinical differential diagnosis included telangiectasiamacularis eruptiva perstans, connective tissue dis-ease, erythema ab igne, and capillary malformation.A punch biopsy specimen revealed papillary dermalinterstitial histiocytic inflammation and multinucle-ated giant cells with elastic fiber phagocytosis in aninterstitial and vaguely palisaded granulomatouspattern (Fig 2).

Patient 2 is a 62-year-old nonsmoking man with ahistory of hypertension, gastric reflux, and hyperlip-idemia who presented with a 3- to 4-month history ofmild, mottled erythema on the chest and arms.Symptoms included burning and pruritus exacer-bated byheat and sunlight. A punch biopsy specimenwas significant for dilated vessels, mild superficialperivascular lymphocytic inflammation, and smallfoci of elastic fiber phagocytosis.

These cutaneous and histopathological findingsare consistent with a rare clinical variant of MDEthat manifests as persistent reticular erythema. Anotable middle-aged male predominance has beenobserved in previously reported cases.4 Variants ofMDE may clinically appear similar to diffusegranuloma annulare, actinic granuloma, or annu-lar elastolytic granuloma. These entities may rep-resent variations on the spectrum of a single

disease process leading to mid-dermal elastic tis-sue loss.3

Histopathologically, MDE presents with mid-dermal loss of elastic fibers, discrete inflammatoryinfiltrates, macrophages engulfing elastic fibers, andscattered giant cells. Reticular variantsmay havemoreprominent perivascular lymphocytic infiltrates.1 Amid-dermal decrease in elastin, but not fibrillin-1,immunoreactivity has been observed.1

The origin of MDE is unclear; however, relation-ships to ultraviolet radiation, smoking, numerousinflammatory diseases, copper abnormalities, de-creased serum elastase inhibitor and increasedelastases, low lysyl oxidase activity, and antielastinantibodies have been suggested.1,2 Mid-dermalmatrix metalloproteinase-9 and -1 activity may beincreased secondary to ultraviolet radiation result-ing in elastolysis and subsequent phagocytosis.1,2 Ithas also been suggested that actinically damagedelastin is an antigenic stimulus for consumption byhistiocytes in similar entities.5 MDE has beenreported after inflammatory events and may beassociated with autoimmune disease.1 Effectivetreatment has not been established; however, sunprotection is recommended.1