Dowling-Dowling-DegosDegos with with

AcantholysisAcantholysis: A Rare Case: A Rare Case

of of Galli-GalliGalli-Galli Disease Disease

Julianne Mann, MDJulianne Mann, MD

Eric Simpson, MD, MCREric Simpson, MD, MCR

History of PresentationHistory of Presentation

•• 75 year old previously healthy Caucasian female75 year old previously healthy Caucasian female

•• 35 year 35 year h/oh/o of widespread hyperpigmented macules of widespread hyperpigmented macules

- first appeared on thighs- first appeared on thighs

- progressed to involve back, neck, and arms- progressed to involve back, neck, and arms

•• 2-3 year 2-3 year h/oh/o pruritic, hyperkeratotic, tan-colored papules pruritic, hyperkeratotic, tan-colored papules

on the extensor and flexural surfaces of extremities,on the extensor and flexural surfaces of extremities,

neck, trunkneck, trunk

History of Present IllnessHistory of Present Illness

•• A previous biopsy done in 2008 had shown focalA previous biopsy done in 2008 had shown focal

acantholyticacantholytic dyskeratosis, and she had been given a dyskeratosis, and she had been given a

diagnosis of Groverdiagnosis of Grover’’s diseases disease

•• Previous treatments included:Previous treatments included:

-Triamcinolone 0.1% cream (transient improvement)-Triamcinolone 0.1% cream (transient improvement)

-A several month course of tetracycline (no help)-A several month course of tetracycline (no help)

•• Family HistoryFamily History: Brother with similar papules limited to: Brother with similar papules limited tothe lower extremities which appeared in middle age.the lower extremities which appeared in middle age.

•• Past Medical HistoryPast Medical History::

- Actinic - Actinic keratoseskeratoses

- Osteoarthritis- Osteoarthritis

- HTN, - HTN, hyperlipidemiahyperlipidemia

- Glaucoma- Glaucoma

- Depression- Depression

- GERD- GERD

•• Physical Exam: Physical Exam: BP 154/94 HR 88 RR 14

•• Medications: Medications:

- HCTZ- HCTZ

- - ParoxetineParoxetine

- - AtorvastatinAtorvastatin

- - EsomeprazoleEsomeprazole

- - BimatoprostBimatoprost

Differential DiagnosisDifferential Diagnosis

•• DarierDarier’’s diseases disease

•• Dowling-Dowling-DegosDegos disease disease

•• EB Simplex with Mottled PigmentationEB Simplex with Mottled Pigmentation

•• Disseminated superficial actinicDisseminated superficial actinic

porokeratosisporokeratosis

•• Atypical GroverAtypical Grover’’s diseases disease

Diagnosis:Diagnosis:

Galli-GalliGalli-Galli Disease Disease

Galli-GalliGalli-Galli Disease Disease

•• Originally reported by Originally reported by BardachBardach, , GebhartGebhart, and Luger in, and Luger in

1982, who described the disease in two brothers1982, who described the disease in two brothers

•• A rare A rare acantholyticacantholytic variant of Dowling- variant of Dowling-DegosDegos Disease, Disease,

an autosomal dominant an autosomal dominant genodermatosisgenodermatosis

•• Approximately 12 cases reported in the literatureApproximately 12 cases reported in the literature

Galli-GalliGalli-Galli Disease: Clinical Findings Disease: Clinical Findings

•• M>F, age range 15-56 yrsM>F, age range 15-56 yrs

•• Reddish-brown, hyperkeratotic, scaly, pruritic papulesReddish-brown, hyperkeratotic, scaly, pruritic papules

•• Confluent, reticulated hyperpigmented maculesConfluent, reticulated hyperpigmented macules

•• Involvement of trunk, neck, and both flexor and Involvement of trunk, neck, and both flexor and extensorextensorsurfaces of the extremities (vs. Dowling surfaces of the extremities (vs. Dowling DegosDegos))

•• No No perioralperioral scars, scars, palmarpalmar pits, or nail changes pits, or nail changes

•• +/- Peripheral eosinophilia+/- Peripheral eosinophilia

Gilchrist 2008; Bardach 2001

Clinical DDx of Clinical DDx of Galli-GalliGalli-Galli Disease Disease

•• Dowling-Dowling-DegosDegos Disease - KRT5 Disease - KRT5•• Reticulated hyperpigmentation mainly in flexures, Reticulated hyperpigmentation mainly in flexures, perioralperioral pitted scars pitted scars,,

comedocomedo-like papules-like papules ( (““dark dotsdark dots””))

•• EB Simplex with Mottled Pigmentation - KRT5EB Simplex with Mottled Pigmentation - KRT5•• Widespread reticulated hyperpigmentation, Widespread reticulated hyperpigmentation, skin fragilityskin fragility (present at birth), (present at birth),

blistering, progressive blistering, progressive palmoplantarpalmoplantar hyperkeratosis hyperkeratosis

•• Reticulate Reticulate AcropigmentationAcropigmentation of Kitamura of Kitamura - - KRT5KRT5•• Acral reticulated hyperpigmentation, Acral reticulated hyperpigmentation, palmarpalmar pits pits, breaks in , breaks in dermatoglyphsdermatoglyphs

•• DyschromatosisDyschromatosis SymmetricaSymmetrica HereditariaHereditaria - DSRAD - DSRAD•• Symmetrical reticulated Symmetrical reticulated hyper- and hypopigmentationhyper- and hypopigmentation of extremities, usually of extremities, usually

presents by age 6yo, patients usually presents by age 6yo, patients usually AsianAsian..

•• DarierDarier’’s Disease s Disease –– ATP2A2 ATP2A2•• Hyperpigmented, hyperkeratotic papules in Hyperpigmented, hyperkeratotic papules in seborrheic distributionseborrheic distribution, dorsal, dorsal

hands and hands and palmspalms involved, involved, dystrophic nailsdystrophic nails, white papules on , white papules on palatepalate

Galli-GalliGalli-Galli Disease: Histopathology Disease: Histopathology

•• Epidermal Epidermal acanthosisacanthosis and hyperkeratosis and hyperkeratosis

•• Elongated epidermal Elongated epidermal reterete ridges with bud-like ridges with bud-like filiformfiliformprojections, projections, suprapapillarysuprapapillary thinning thinning

•• Hyperpigmentation of basal layerHyperpigmentation of basal layer

•• SuprabasilarSuprabasilar acantholysisacantholysis !! linear clefts linear clefts

•• Mixed dermal inflammatory infiltrateMixed dermal inflammatory infiltrate

Sprecher 2007

PathogenesisPathogenesis

•• Mutation in the Mutation in the KRT5 (Keratin 5) geneKRT5 (Keratin 5) gene on chromosome on chromosome12q reported in patients with 12q reported in patients with Galli-GalliGalli-Galli disease is disease isbelieved to lead to:believed to lead to:

!! abnormal intermediate filament cytoskeletonabnormal intermediate filament cytoskeleton

!! compromise in the structural integrity of basal layercompromise in the structural integrity of basal layerkeratinocytes keratinocytes !! suprabasilarsuprabasilar acantholysisacantholysis

•• Hyperpigmentation seen in Hyperpigmentation seen in Galli-GalliGalli-Galli, Dowling-, Dowling-DegosDegos,,and EBS-MP suggests that keratin 5 probably plays aand EBS-MP suggests that keratin 5 probably plays arole in melanin traffickingrole in melanin trafficking

Liao et al 2007; Sprecher 2007

TreatmentTreatment

•• Treatment of Treatment of hyperkeratosishyperkeratosis is challenging: is challenging:

- - TretinoinTretinoin and urea cream are irritating and often and urea cream are irritating and often

exacerbate the hyperkeratosisexacerbate the hyperkeratosis

- Oral retinoids not helpful- Oral retinoids not helpful

•• Therapies reported to improve Therapies reported to improve prurituspruritus have been slightly have been slightly

more successful:more successful:

- NBUVB- NBUVB

- Prednisone or topical corticosteroids- Prednisone or topical corticosteroids

- Cyclosporine- Cyclosporine

Gilchrist 2008; Braun-Falco 2001

SummarySummary

•• Galli-GalliGalli-Galli disease is an disease is an acantholyticacantholytic variant of Dowling- variant of Dowling-

DegosDegos disease disease

•• Galli-GalliGalli-Galli disease should be included in: disease should be included in:

•• The clinical DDx of reticulate hyperpigmentationThe clinical DDx of reticulate hyperpigmentation

•• The histologic DDx of focal The histologic DDx of focal acantholysisacantholysis +/- +/-

dyskeratosisdyskeratosis

•• Keratin 5 mutations are found in Keratin 5 mutations are found in Galli-GalliGalli-Galli, Dowling-, Dowling-DegosDegos,,

and EBS with mottled hyperpigmentationand EBS with mottled hyperpigmentation

ReferencesReferences

BardachBardach H, H, GebhartGebhart W, Luger T. W, Luger T. GenodermatosisGenodermatosis in a pair of brothers: Dowling- in a pair of brothers: Dowling-DegosDegos,,Grover, Darier, Hailey-Hailey, or Grover, Darier, Hailey-Hailey, or Galli-GalliGalli-Galli disease? disease? HautarztHautarzt 1982; 33(7): 387-83. 1982; 33(7): 387-83.

Braun-Braun-FalcoFalco M, M, VolggerVolgger W, Borelli S, Ring J, W, Borelli S, Ring J, DischDisch R. R. Galli-GalliGalli-Galli disease: an unrecognized disease: an unrecognizedentity or an entity or an acantholyticacantholytic variant of Dowling- variant of Dowling-DegosDegos disease? disease? J Am J Am AcadAcad DermatolDermatol.. 2001 2001Nov; 45(5):760-3.Nov; 45(5):760-3.

El El Shabrawi-CaelenShabrawi-Caelen L, L, RuttenRutten A, A, KerlKerl H. The Expanding Spectrum of H. The Expanding Spectrum of Galli-GalliGalli-Galli Disease. J Disease. JAm Am AcadAcad DermatolDermatol 2007; 56: S86-91. 2007; 56: S86-91.

Gilchrist H, Jackson S, Morse L, Gilchrist H, Jackson S, Morse L, NicotriNicotri T, Nesbitt LT. T, Nesbitt LT. Galli-GalliGalli-Galli disease: A case report with disease: A case report withreview of the literature. J Am review of the literature. J Am AcadAcad DermatolDermatol. 2008 Feb; 58(2): 299-302.. 2008 Feb; 58(2): 299-302.

Liao H, Zhao Y, Liao H, Zhao Y, BatyBaty DU, McGrath JA, DU, McGrath JA, MellerioMellerio JE, McLean WH. A heterozygous JE, McLean WH. A heterozygous frameshiftframeshiftmutation in the V1 domain of keratin 5 in a family with Dowling-mutation in the V1 domain of keratin 5 in a family with Dowling-DegosDegos disease. J Invest disease. J InvestDermatolDermatol 2007; 127: 298-300. 2007; 127: 298-300.

RuttenRutten A, A, StaubStaub T. T. MorbusMorbus Galli-GalliGalli-Galli: A further case report. : A further case report. AktAkt DermatolDermatol 1995;21: 255-7. 1995;21: 255-7.

SprecherSprecher E, E, IndelmanIndelman M et al. M et al. Galli-GalliGalli-Galli disease is an disease is an acantholyticacantholytic variant of Dowling- variant of Dowling-DegosDegos Disease. Br J Disease. Br J DermatolDermatol 2007; 156: 572-4. 2007; 156: 572-4.