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Cutaneous manifestations in solid organ transplant recipients FM O’ Reilly Zwald MD, MRCPI O’Reilly Comprehensivc Dermatology, INC Piedmont Cancer

End-stage organ disease SKIN CHANGES


• pallor, sallow, hyperpigmented • elastosis • ecchymoses • xerosis • half-and-half nails • pruritus

• Perforating disorders • Metastatic calcification • Calciphylaxis • Porphyria cutanea tarda • Pseudoporphyria

INFECTION • • • • • • • •


• • • • •


FUNGAL • Superficial fungi • Deep fungal infections e.g. candida, cryptococcus, aspergillus. • Dimorphic fungi e.g. histoplasma, coccidiomycosis, blastomycosis • Other opportunistic fungi e.g. alternaria, fusarium, mucor, rhizopus, absidia

Risk Periods After Transplant • 0-30 days • 30-180 days: greatest period of immunosuppression • 6+ months

Time Course for Viral Infections after Solid Organ Transplant

Snydman, CID 2001; 33(Supp1): S5-8.

Time Course for Fungal Infections after Solid Organ Transplant

Infections to always worry about • PCP • Adenovirus

• BK virus • Pneumococcus

• HHV-6 • Late CMV Disease

• Legionella • Mycobacteria

• Epstein-Barr virus (PTLD)

• Fungal infections • Nocardia

Risk Factors for Invasive Fungal Infection • • • • • •

Prolonged pre-transplant dialysis Rejection Diabetes Older age Steroids CMV reactivation Singh et al 2003; Riza et al. 2002; Baddley2001;

Incidence Skin Cancer in Transplant Patients SCC


SCC of lip


BCC Melanoma

?10-fold ? 3 fold

Other Skin Cancers in Transplant Patients • • • • • • •

Kaposi’s Sarcoma Merkel Cell Carcinoma Angiosarcoma Verrucous Carcinoma Atypical Fibroxanthoma Leiomyosarcoma CTCL

Incidence of Cancer in Pediatric Transplant Patients • Cincinnati Registry 1968-1994 • 392 tumors in 383 pediatric transplant patients: - Lymphomas: 53% - Skin Cancer: 19% - Sarcomas: 4% - Kaposi’s: 2% Penn I. Transplant Proc 1994;26(5):2763

Incidence of Skin Cancer in Pediatric Transplant Patients • 74 skin tumors in pediatric recipients – 14 presented in childhood – SCC (65%), Melanoma (15%), BCC (14%)

• Lip SCC common (30% of skin cancer) • Aggressive behavior – 12% nodal metastases – 10% mortality rate

CASE 1 • A liver transplant recipient presents with jaundice and associated pruritus. • Skin lesions developed over 6 weeks

Perforating Dermatoses • Transepidermal proliferation of collagen, elastin • Umbilicated papules with a central keratotic plug • Koebnerization • Associated with DM, uremia. • Resolves with resolution pruritus

CASE 2 A 56 yr old AA presented with multiple pruritic lesions on the trunk and extremities which appeared suddenly over two weeks, one month after successful kidney transplant surgery

CASE 3 A 42 year old man with ESRD developed the acute onset of painful, erythematous indurated plaques on the extremities 6 days after vascular rejection of a cadaveric kidney transplant due to renal vein thrombosis.

Nephrogenic Fibrosing Dermopathy • Scleromyxedema-like illness of renal disease • Le Boit Arch Dermatol 2003 (139) 928 • Fibroplasia- increase in collagen and mucin in the dermis • Etiology- infective? Drug induced fibroplasia? Anti-phospholipid antibodies?

CASE 5 A 53 year old white HIV- negative man with a 5 year history of massive panlobular emphysema underwent left lung transplantation. Three episodes of allograft rejection necessitated IV methylprednisone. Severe stenosis of the left main bronchus developed followed by an asymptomatic nodular lesion of the left ear, then similar lesions on the left side of the chest

Red, brown nodular lesions on the chest

Kaposi’s sarcoma • HHV8 seropositive patient (HIV neg) with skin and graft KS after lung transplantation • Tumors localized to sites of previous trauma, implying the involvement of the Koebner phenomenon • PCR identified DNA of KSHV in involved skin • HHV8 present 95% cases all types of KS • Seropositive prior to transplantation • ? Sensitivity of KSHV to antivirals (JAAD 1999 (2): 40;2)

NAIL DISORDERS Absence of lunula

H/D (%) 58

Tx (%) 35

Splinter hemorrhage Onychomycosis Leukonychia Half-and-half nails Terry’s nails Koilonychia Muerchke’s nail

25 35 19 14 6 5 1

7 26 44 4 6 2 5

FUSARIUM • Fusarium sp. molds that are prevalent in the soil and air • Fusarium infection increasing in frequency among immunocompromised hosts • Multiple red or gray macules with central ulceration or black eschar • Consider in febrile patient with neutropenia and hematologic malignancy • Most lesions fail to respond to anti-fungal therapy unless there is resolution of the neutropenia

Case 7 A 64 year old woman had a 2 month history of an eruption on her left arm. She had severe COPD and had been taking 30 mgs prednisone twice daily for two years.

Aspergillus • Among the most ubiquitous fungi • Respiratory tract primary portal of entry • Primary cutaneous aspergillosis occurs in the immunocompromised • Identical to Fusarium in tissue, therefore, culture mandatory • Amphotericin B (nephrotoxic), caspofungin (JAAD, 2002;46:6)

CASE 8 A 60 year old man with HIV, presented with an asymptomatic bleeding nodule on his nose, which had been present for approximately 6 weeks.

Merkel Cell Carcinoma (MCC) in Transplant Patients • 52 cases reported (1999) – Aggressive, younger patients – 65-75% metastatic rate; >50% mortality

• Melanoma : MCC = 6:1 in immunosuppressed • Melanoma : MCC = 65:1 in general population Source: Cincinnati Transplant Tumor Registry (41/52 total cases) Penn, I et al. Transplantation 1999;68(11):1717


Cutaneous Appendageal Tumors in Transplant Recipients • High frequency in organ transplant recipients • Sebaceous, eccrine, apocrine tumors from transplant patients were more likely to be malignant • Sebaceous tumors, especially sebaceous carcinoma significantly increased in organ transplant recipients (JAAD 2003;48:401-8)

Pediatric Transplant Dermatology

Pediatric Transplant Dermatology Drug S/E



Striae distensae


Increase of nevi

Iatrogenic acne

Anogenital warts




Pyogenic granuloma

Gingival hyperplasia

Herpes simplex

Skin tags

Herpes zoster Tinea versicolor Dermatophytoses Bacterial infections

Melanocytic nevi in Pediatric transplant recipients • Eruptive nevi has been reported after renal transplantation • Immunosuppression suggested to favor melanocytic proliferation • Occurs after age 7 even if tx in infancy • Dermoscopy- peripheral rim of brown globulesindicates melanocytic proliferation • Viewed without anxiety though strict f/up necessary

CASE 10 A 28 year old woman with ESRD and DM presented to the emergency department with exquisitely painful plaques on the lower extremities

Case 11 A 23 year old woman S/P renal transplant presents with a four month history of a progressive pruritic eruption involving the upper half of the body. The lesions began on the face and extended to the neck and chest

Eruptive Keratoacanthomas • Variants of multiple KA include Ferguson Smith type and EK of Grybowski • Generalized pruritic eruption of thousands of disseminated 2-6 mm KA with ectropion and intra-oral involvement c/w EK of Grybowski • Multiple KA has a higher incidence in the immunosuppressed

CASE 12 A 64 year old AA female S/P renal tx 1994 presented with a pruritic erythematous eruption that intensified to generalized erythroderma with superimposed indurated papules and nodules over the period of a month

Post-transplant primary cutaneous T- lymphoma • T cell PTLD present as a late complication of solid organ transplantation • Frequency 3-14% in immunosuppressed • Highly aggressive tumors • Function of EBV in the onset of T cell lymphoma in transplant recipients obscure • HTLV-I, II may have a role in pathogenesis

CASE 13 • 31 year old male S/P a kidney transplant in 1984. • 1990 - SCC of the lower lip (Mohs). • 1994 - multiple biopsies of the dorsal hands revealed SCCs; he was treated with radiation. • The lesions recurred, he was offered bilateral amputations (large lesions), but refused surgery. Acquiesced one year later when he re-presented with 3 cm nodules eroding to the palm • 6 mths later presented with an axillary mass and an eruption on the anterior chest

Cutaneous SCC with zosteriform metastasis in a transplant recipient • SCCs metastasizing to the skin usually from internal organs or oral cavity • Less often the primary tumor is a distant site in the skin • More uncommon for a primary cutaneous SCC to metastasize in a zosteriform distribution • Zosteriform appearance of metastatic disease reported where primaries included prostate, lung, bladder.

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