Skin Lesions of the Immuno-Compromised

Skin Lesions of the Immuno-Compromised
Immuno-compromised patients, particularly those with HIV/AIDS, are recognised as having a particular spectrum of
cutaneous disease which varies from that seen in immuno-competent people. In particular there is a range of infectious
diseases, inflammatory conditions and tumours which have an increased incidence and different presentation to that
commonly seen. In the case of HIV/AIDS this spectra changes as the disease evolves and different therapeutic regimes
come into place. This has resulted in developed countries shifting the emphasis to the long term complications of
HIV such as cancer, co-infection with other viruses such as a Hepatitis C, and the metabolic effects of Highly Active
Antiretroviral Therapy, (HAART). In developing countries the focus remains on the opportunistic infections which
develop, though these infections still remain a cause of clinical presentation in Australia.
Inflammatory Disorders: There is a range of inflammatory skin disorders which are more frequent and/or are more severe in
AIDS patients, though this range of disorders may be less common in other types of immuno-compromised individuals.
Seborrhoiec Dermatitis: Up to 85% of HIV patients will develop
seborrhoiec dermatitis. In addition to the usual clinical appearance
there may be other patients who develop an exaggerated form
of the disease such as facial plaques or a greater involvement of
extra facial sites. Patients presenting with sudden exaggerated
seborrhoiec dermatitis or patients with previously stable disease who
develop sudden worsening of their seborrhoiec dermatitis should be
suspected of having an underlying HIV infection.
Eosinophilic Folliculitis: In addition to its know association with
HIV/AIDS this disorder is also described in patients with lymphoma/
leukaemia and/or in stem cell transplant recipients. It is a rare
disorder outside of this population of immuno-suppressed patients.
The disease is characterised by follicular papules which are usually
excoriated due to the intense pruritis which accompanies their
development. Affected patients usually have a CD4 + count of <200
cells/cumm. There may be an associated peripheral eosinophilia.
Psoriasis: Psoriasis in AIDS patients is often more severe and is
associated more frequently with nail dystrophy, arthritis and Reiter’s
disease, though the overall incidence is probably not increased.
Vasculitis: A polyarteritis nodosa-like vasculitis with associated
peripheral neuropathy and digital ischemia can occur though it is
usually confined to the skin and not systemic. Erythema elevatum
diutinum also has an increase incidence in AIDS patients who have a
CD4 + count of <200 cells /cumm.
Reiter’s Disease: HIV infected patients with HLA/B27 often
develop Reiter’s disease after genito-urinary or gastro-intestinal
infection. Some authorities suggest that patients with newly
diagnosed Reiter’s disease should be considered for HIV testing.
Miscellaneous: A number of other inflammatory dermatoses have
an increased incidence in HIV/AIDS patients including pityriasis rubra
pilaris, acquired icthyosis, photo-sensitivity, porphyria cutanea tarda,
alopecia and atopic dermatitis (in children).
Infectious Diseases: Immuno-compromised patients have a greater susceptibility to infectious disease. Bacterial infections are
often more severe and there can be infection by bacteria which are usually not pathogenic. In addition to this general susceptibility
there are some diseases which a particular association with immuno-compromised patients, particularly HIV/AIDS patients.
Herpes Simplex Virus: HSV infection in the immuno-compromised
can be characterised by chronic non-healing, deep ulcerating lesions
which can also involve the peri-anal region, genitalia and tongue.
Herpes Zoster: The lesions of Zoster may effect multiple
dermatomes and have an ulcerative, chronic and verrucous
manifestation. There is often bacterial supra-infection and the disease
process can be complicated by acyclovir resistance, therapeutic
failure and multiple recurrences.
Molluscum Contagiosum: This disease is particularly common in
children who are immuno-compromised (including AIDS). The lesions
in immuno-compromised people can be large (>1cm), coalescent and
disfiguring. The lesions may be resistant to treatment and particularly
affect the face, neck and inter-trigonous zones.
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Human Papilloma Virus: The lesions of HPV tend to be more
widespread including formation of multiple verrucae. The verrucae
may coalesce into large plaques. There is an associated higher risk of
developing cervical and anal intraepithelial neoplasia (CIN/AIN).
Epstein-Barr Virus: Oral hairy leucoplakia occurs commonly
in individuals with HIV infection, affecting approximately 25%,
and is often an early sign of such infection. Its development in the
absence of anti-retroviral therapy is a predictor of rapid decline and
progression to AIDS.
Cytomegalovirus: CMV can cause ulcers, verrucous and/
or pruritic papules which may progress to vesicles, morbilliform
eruptions and hyperpigmented indurated plaques. Cutaneous
involvement by CMV is less common though in comparison to its
involvement of other sites, eg retinitis, oesophagitis and colitis.
Skin Lesions of the Immuno-Compromised continued
Bacillary Angiomatosis: This is an unusual disorder which is
infrequently seen outside of the setting of immuno-suppression/
AIDS. The histologic appearance is of a vaso-proliferative disorder in
which a proliferation of capillaries and venules is seen in association
with numerous neutrophils and cellular debris. There are associated
clumps of gram- negative bacteria which are of the Bartonella genus.
Clinically there is formation of superficial angiomatous papules, with
more advanced lesions forming plaques or deep subcutaneous
nodules, sometimes with ulceration. The superficial papules may
resemble pyogenic granulomas. They are usually seen in HIV infected
patients who have a CD4 + count of <200 cells/cumm.
Demodicosis: In HIV/AIDS patients infection by demodex mites can
produce a rosacea-like eruption, usually involving the head and neck
regions.
Mycobacteria: Infection with mycobacteria can produce
erythematous papules and nodules, ulcers, verrucous plaques and
deep nodules. Pruritis is often absent and patients may be febrile.
Histologically there may be large numbers of organisms, often filling
the cytoplasm of macrophages, and there may be little evidence of a
suppurative or granulomatous reaction.
Syphillis: In immuno-suppressed patients there may be rapid
progression to nodulo-ulcerative forms. There may be a papular
eruption which mimics molluscum contagiosum. Lues Maligna can
develop, this is an aggressive widespread variant of secondary
syphillis which has a prodrome of fever, headache and myalgia in
association with a papulo-pustular eruption.
A
B
Candida: Candida is the infection most frequently encountered
in HIV/AIDS patients and 90% of AIDS patients will develop oral
candidiasis. Perleche, with painful fissuring at the oral commisures,
and persistent candidil infections of inter-trigonous zones are features
of the more severe clinical manifestation seen in immuno-suppressed
patients. Other complications include chronic paronychia and
onychodystrophy.
Dermatophytoses: There is an increased incidence of
dermatophytoses in immuno-suppressed patients and the clinical
appearance may be atypical. In particular the rashes are often more
widespread and resistant to therapy. An additional complication is
that the areas of superficial fungal infection may act as an avenue into
deeper tissues for more serious bacterial pathogens.
Cryptococcus: Patients with disseminated cryptococcus may
develop cutaneous lesions as part of this multi-system process.
The cutaneous lesions are often represented by multiple translucent
dome-shaped papules with central umbilication. These nodules
particularly affect the face and they may clinically resemble
molluscum contagiosum.
Scabies: Scabies infections tend to be more severe due to
the decreased cell mediated immunity in immuno-suppressed
individuals. In addition to the development of the typical crusted
papule of scabies infection there may be a more generalised pruritic
dermatitis and progression to formation of large keratotic and
crusted plaques, though the latter sometimes may not be pruritic.
The scabies burrows are often less apparent in the immunocompromised patient and there may also be involvement of other
sites such as the ears, face and scalp. There can be involvement
of nails including marked subungal involvement with gross nail
thickening.
Molluscum Contagiosum
A. This is a large lesion showing
expansion into the mid dermis.
B. Higher power showing formation
of molluscum bodies (arrow) and
their extrusion into the overlying
keratotic layer.
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Skin Lesions of the Immuno-Compromised continued
Neoplasms: There is a range of neoplasms which occur more frequently in immuno-compromised people. Treatment may be
particularly problematic in those patients having therapeutic immuno-suppression, eg transplant recipients, as treatment of the
tumour is often aided by reducing the immuno-suppression. The high incidence of sun damaged skin in Australian residents is
also a contributing factor to disease incidence.
Squamous Cell Carcinoma and Basal Cell
Carcinoma: Both of these tumours occur more
frequently and in younger people. A greater range of
clinical sites is involved and the ratio of squamous cell
carcinomas to basal cell carcinomas is reversed, with
squamous cell carcinomas being more common. The
risk factors for development of these tumours are the
same as those for the general population, ie fair skin and
high sun exposure. There is also an increased risk of
metastatic disease, including cases of metastatic basal
cell carcinoma. Pre-cursor lesions, namely solar keratosis
and squamous cell carcinoma in-situ/Bowenoid solar
keratosis, also have a higher incidence.
Lymphoma: An increased number of B and T cell
non-Hodgkin’s lymphomas occur in immuno-suppressed
patients, particular in HIV/AIDS patients with a CD4 +
count of <200 cells/cumm. The lymphomas tend to be
of intermediate to high grade, rather than low grade, and
can be associated with development of ulcerating lesions
or with a diffuse disease which mimics a panniculitis.
Most lymphomas are of B cell type though there is still
an increased incidence of mycosis fungoides T cell
lymphoma. Lymphomas in the immuno-suppressed
tend to have an earlier age of onset and to present at a
more advanced stage. There is a greater incidence of
extra-nodal involvement and, in addition to skin, other
sites with more frequent involvement include the central
nervous system and gastro-intestinal tract. There is
also a reported increased incidence of Malt lymphomas
involving the lungs, stomach and salivary glands in HIV
infected children.
Kaposi’s sarcoma: This vascular tumour was first described in 1872
with this initially described ‘classical form’ of the disease occurring
particularly in people of eastern European and Mediterranean origin,
and is not associated with HIV. Subsequently three other clinical types
of Kaposi’s sarcoma have been described, an African (endemic) form,
an immuno-suppression related form and an HIV associated form.
Kaposi’s sarcoma can occur at any stage of infection with HIV and does
not correlate with the degree of immuno-suppression. Initially one third
of HIV infected patients developed Kaposi’s sarcoma however since the
utilisation of HAART the incidence has decreased to approximately 10%.
The lesions evolve through stages of patch, plaque and nodule formation.
The initial patch stage may resemble a bruise. These lesions can
particularly occur along skin lines, sometimes in a pityriasis rosea-like
pattern, and in areas of local trauma. The histological changes can also
be subtle and difficult to differentiate from benign vascular proliferations
such as telangiectasias and pigmented purpuric dermatoses. As the
disease progresses it forms larger plaques and nodules and becomes
easier to recognise clinically and histologically. In non-HIV immunosuppressed patients it has been described in patients receiving steroid
therapy, such as for bullous pemphigoid, pemphigus and hepatitis C,
and in patients receiving chemotherapy.
Patients given interferon for lymphoma have also developed Kaposi
sarcoma. It is described as a complication in renal and bone marrow
transplant patients, though is rare in cardiac transplant patients.
Kaposi sarcoma can develop within a short time of commencing
immuno-suppressive therapy and may regress spontaneously following
cessation of that therapy. In immuno-suppressed and HIV/AIDS patients
the disease is often more aggressive and multifocal, with involvement of
multiple organs, and it can be rapidly progressive. The degree of internal
involvement does not necessarily correlate with the degree of cutaneous
involvement.
Table 1. Cutaneous manifestations of AIDS
Infections
Neoplasms
Viral: molluscum contagiosum, herpes simplex, herpes zoster,
verruca vulgaris, condylomas, cytomegalovirus, oral hairy
leukoplakia, Kaposi’s sarcoma
Kaposi’s sarcoma, cutaneous lymphomas, Bowen’s disease,
squamous and basal cell carcinomas, cutaneous melanomas
Bacterial: mycobacterial infections, more usual bacterial infections,
bacillary angiomatosis
Dermatoses
Spirochetal: syphillis
Fungal: candidosis, dermatophytosis, histoplasmosis,
cryptococcosis, tinea versicolor, phaeohyphomycosis, nocardiosis,
mucormycosis, Penicillium marneffei infection
Protozoa: acanthamebiasis, pneumocystosis
Arthropod: scabies, demodicosis
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Psoriasis, seborrhoiec dermatitis, pityriasis rubra pilaris,
acquired ichthyosis, asteatosis, porokeratosis, vasculitis, folliculitis,
contact dermatitis, photosensitivity, vitiligo,
yellow nail syndrome, papular eruption, idiopathic pruritis,
a chronic diffuse dermatitis, severe drug reactions, alopecia,
palmoplantar keratoderma, porphyria cutanea tarda,
acrodermatitis enteropathica, neutrophilic eccrine hidradenitis
Reproduced from Weedon’s Skin Pathology, Third edition, Dr David Weedon
Skin Lesions of the Immuno-Compromised continued
Scabies; numerous organisms are seen with associated hyperkeratosis.
In usual scabies the pathologist is fortunate to see one organism per biopsy
section.
Kaposi sarcoma; cellular, vascular tumour with spindle cell component, red
blood cell extravasation and slit like vascular spaces.
Effects of Treatment of HIV: Since the introduction of
highly active antiretroviral therapy (HAART), there has been
a marked decrease in opportunistic infections and some
neoplasms. HAART can markedly suppress viral replication
leading to increasing CD4 + lymphocyte counts and an
associated reduction in morbidity and mortality. There is an
increased life expectancy as a result of HAART and a reduction
in the incidence of Candidiasis, superficial dermatophyte
infection, deep mycoses, mycobacterial infection, crusted
(Norwegian) scabies, Herpes simplex, the verrucous lesions
of herpes zoster, oral hairy leucoplakia, eosinophilic folliculitis,
lymphoma and Kaposi sarcoma. The prevalence of papilloma
virus and pox virus infections have increased however.
Paradoxically there can also be a worsening of some
diseases or sudden clinical manifestation of diseases due to
HAART therapy and the associated rise in the CD4 + cell
count, this is referred to as the immune reconstitution
syndrome or immune recovery syndrome.
Clinical infections which may worsen or suddenly appear
include those due to mycobacteria (TB, atypical TB and
leprosy), herpes zoster virus, cytomegalovirus, hepatitis B
and C and cryptococcus. There may also be a temporary
worsening of eosinophilic folliculitis. Other inflammatory
disorders which may develop include psoriasis, sarcoidosis,
photosensitivity reactions, lupus erythematosus (systemic,
tumid) and dishydrotic eczema. Complications of HAART in
which protease inhibitors are used as part of the multi-agent
therapy include lipodystrophy and paronychia. Neoplasms
which may occur as a result of therapy include Kaposi
sarcoma and multiple eruptive dermatofibromas. It may be
clinically difficult to distinguish between sudden worsening
of opportunistic infections, due to the immune reconstitution
syndrome, and drug toxicity related to therapy.
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Dr Kevin Trown Anatomical Pathologist.
T: 9476 5281 E: [email protected]