Itchy Skin in HIV

[Michelle Roland, a 4th-year medical student, is starting
Internal Medicine residency at the University of California
San Francisco/San Francisco General Hospital in June.]

Introduction

[Note: Much of the clinical and research information
contained in this article was provided by physician
investigators in the Dermatology department at San Francisco
General Hospital. We would like to thank Toby Maurer, M.D.,
and Tim Berger, M.D., for their help in educating us and
contributing to the research cited in this article.
Appointments for evaluation and treatment of HIV-associated
skin problems can be made at the San Francisco General
Hospital Dermatology Clinic by calling 415/206-4470.]

Itchy skin rashes are very common in people with HIV
infection. The medical term for itch is pruritus. The
specific cause of the itch may be related to HIV-induced
immunosuppression or, less commonly, to specific organ
disease resulting from opportunistic infections, cancer, or
non-HIV related illness. The incidence of many of the
diseases which cause itch increases as the T-helper cell
(CD4) count decreases, thus itch is often associated with
more severe immunocompromise.

Doctors Toby Maurer and Tim Berger, researchers at San
Francisco General Hospital, examined many people with HIV who
had itchy skin and found that a diagnosis could be made with
a relevant clinical history, physical examination, and
sometimes a skin biopsy or other studies, in approximately
90% of their patients. Once diagnosed, the majority of these
conditions can be treated. Some are quite responsive to
therapy, while others may be resistant to currently available
treatment options.

The most common causes of itch in HIV infection can be
divided into the following categories: 1) scabies and insect
bite reactions, 2) inflammation of the hair follicles
including either eosinophilic or bacterial (staph)
folliculitis, 3) drug reactions, 4) dry skin, 5) a group of
scaly skin disorders including seborrheic dermatitis and
psoriasis, and 6) photosensitivity dermatitis. These terms
will be described in non-medical language in the body of this
article.

Systemic illnesses including renal (kidney), hepatic (liver),
endocrinologic (various hormone systems), hematologic (blood
or bone marrow), neurologic (nervous system) and psychiatric
disorders, may also be associated with itchy skin. The
previously held theory of a "pruritic eruption of HIV," which
proposed that HIV itself caused itch associated with a rash,
has not been supported by investigations at San Francisco
General Hospital.

A cause for itchy skin, which is often extremely distressing,
should be aggressively pursued. Referral should be made to a
dermatologist with experience in this area if the primary
care physician has been unable to make a diagnosis.
Unfortunately, in some cases, no cause or syndrome will be
identified and the patient and health care provider will be
left with the challenge of symptomatic management.

Scabies

Scabies are very common and should always be looked for.
Scabies infections in people with HIV may take one of the
following forms: 1) typical, 2) exaggerated or atypical or 3)
crusted (Norwegian) scabies.(1) Typical scabies cause small
itchy bumps, especially between the fingers, with visible
thin white lines representing burrows. These bumps (also
called papules) can often be found in the genital and skin
fold areas as well. In exaggerated or atypical scabies, there
may be widespread infection with itchy bumps in atypical
areas and none in the more common locations.

In some cases, especially in more immunocompromised
individuals, the scabies infection may become crusted
(sometimes called Norwegian scabies). The lesions are
unusual: there are no bumps, but rather widespread thick
crusts, especially on the scalp, face, back, and under the
nails. The crusts contain very high concentrations of mites
and are extremely contagious. The skin may or may not be
itchy. Serious systemic bacterial infections may occur in
people with crusted scabies as cracks in the skin serve as a
portal of entry into the blood stream for bacteria that
normally inhabit the skin or for hospital-acquired bacteria.

Diagnosis requires (non-painful) skin scrapings and
microscopic identification of the mites or eggs. If the
scrapings do not show evidence of scabies, a skin biopsy from
an area which has not been scratched may be necessary to
confirm the diagnosis. Initial treatment may employ Lindane
(Kwell) cream or lotion(2) or Permethrin (Elimite) cream.(3)
Patients with crusted scabies should be followed carefully
for signs and symptoms of systemic bacterial infection and
treated appropriately with oral or intravenous antibiotics.

Scabies which do not respond to standard treatment, including
crusted scabies, may require an extensive approach such as
the three week regimen advocated by Dr. Timothy Berger at the
San Francisco General Hospital Dermatology Clinic. Permethrin
(Elimite) cream is applied on day one. On day two, Lindane
(Kwell) cream or lotion is used. On days three through seven,
Crotamiton (Eurax) cream or lotion is applied. This entire
three drug course is repeated three times, for a total of
three weeks. According to Dr. Berger, this approach is
approximately 75% effective in eliminating persistent
scabies. After the full three week treatment, if subsequent
skin scrapings show no mites or eggs, the entire home must be
thoroughly cleaned, including vacuuming of all floors and
furnishings, dry cleaning of drapes or curtains, and flea
bombing. Household members should also be treated monthly
with standard anti-scabies medication if they are not
immunosuppressed.

Itch may persist for several weeks after successful
eradication of scabies. The dead mites, eggs, and feces left
in the skin appear to elicit an on-going allergic-type
reaction. If the itch persists beyond several weeks, either
the scabies were not completely eradicated, there has been a
re-infestation, or there may be a second process involved.

Insect Bites

Flea and mosquito bites may be more extensive in people with
HIV infection, eliciting a more severe allergic reaction than
usual. Itchy hive-like bumps on the legs may be insect bite
reactions. Sometimes these bumps will develop into small or
large blisters; a skin biopsy may be required to confirm that
the insect bite reaction is the cause of the lesions.(2)

Treatment of animals in the home, application of insect
repellents, and symptomatic treatment of itch are indicated.
Standard oral anti-itch medications such as the
antihistamines diphenhydramine (benadryl) and hydroxyzine
(atarax or vistaril) may be effective but are sedating. The
most potent anti-itch medication is Doxepin (Sinequan), an
antidepressant used for its potent anti-histamine side
effect. 25-50 mg at night relieves itch and is sedating,
promoting a good night's rest. Topical steroids such as
triamcinalone 0.1% cream or hydrocortisone 1% cream may also
be helpful.

Eosinophilic Folliculitis (EF)

EF is a skin disease which is unique to HIV and is being
recognized more frequently as it is discussed more in the
medical literature. It is an itchy hive-like bumpy rash; each
bump occurs around a hair follicle. The cause of EF is
unknown, but does not seem to be bacterial, fungal, or
related to the common skin mite, Demodex. EF has a
characteristic clinical presentation as well as recently
defined skin biopsy findings.(4) The lesions occur on the
scalp, face, neck, upper trunk and upper arms in people with
advanced HIV infection (fewer than 250-300 T-helper cells).
The skin has often been scratched.

The clinical presentation of itchy bumps around the hair
follicles on the face and trunk appears to be very specific
for EF, thus some experienced clinicians do not believe that
a skin biopsy is necessary to make the diagnosis,
particularly if the patient has failed to respond to systemic
antibiotic treatment. When a skin biopsy is indicated, it is
important that a primary lesion (one which has not been
scratched or secondarily infected) be identified.

Initial standard treatment strategies for EF used to employ
astemizole (Hismanal), a non-sedating antihistamine, or
ultraviolet B (UVB) light therapy. (Note: astemizole should
not be used in combination with the anti-fungal agents
ketoconazole or intraconazole). Although UVB is often
effective, maintenance treatment is required as relapses are
common after termination of treatment.(5) In addition, people
with HIV appear to be at an increased risk for
photosensitivity reactions, including reactions caused by
UVB.(6)

Fortunately, a relatively new anti-fungal drug, itraconazole,
has recently been demonstrated to be effective in EF.(7) The
mechanism of its action is believed to be distinct from its
anti-fungal properties, as no fungus has been consistently
identified in EF. The authors of the itraconazole paper
suggest that a clinical diagnosis should be confirmed by skin
biopsy (although if the lesions are characteristically
located, are centered around follicles, and have not
responded to systemic antibiotics, this may not be
necessary). They recommend initiating itraconazole at 200 mg
a day. This dosage may be increased to 300 or 400 mg daily if
there has not been a significant response after two weeks.
Note that itraconazole should be ingested with food. [The
Conant Medical Group recommends taking itraconazole with an
acidic beverage, for example a Coke or orange juice, followed
by a meal. Patients taking ddI may have inadequate absorption
of itraconazole because of the buffer required with ddI.] As
with the some other anti-fungals, it has many important drug
interactions and must be prescribed carefully and monitored
closely.(8)

Staphylococcal Skin Infections

Another cause of folliculitis in HIV is Staphylococcus aureus
(staph aureus), a common bacteria which infects the skin.
Some people normally carry staph aureus in their noses, where
it does not cause disease but may re-infect the skin and
other parts of the body. In HIV, staph aureus commonly causes
several skin infections, some of which may be itchy.

Folliculitis is the most common infection caused by staph in
people with HIV.(9) It may be confused with EF and should
always be ruled out before a clinical diagnosis of EF is
made. The lesions are usually red bumps containing pus which
are centered around a hair follicle. Sometimes they appear as
small hive-like bumps. The folliculitis occurs most commonly
on the upper trunk or back, legs, and groin. The infection
may become more widespread and form abscesses, boils or
carbuncles. Alternatively, an atypical form of staph
folliculitis which occurs on the scalp, under the arms, or in
the groin appears as large raised deeply red or purple
lesions studded with pus-filled bumps.(2)

Diagnosis requires culture of pus from the lesion. In
uncomplicated cases of staph folliculitis, a short course of
a single oral antibiotic should suffice. The more involved
lesions may require longer courses of antibiotics and the
addition of rifampin (600 mg a day for five to ten days).

Staph aureus may also be involved in secondary infections of
other itchy skin diseases, increasing the itch. It can also
cause a blistering skin infection called bullous impetigo,
which may be mildly itchy. Diagnosis and treatment of bullous
impetigo are the same as for uncomplicated folliculitis.

Drug Reaction

Allergic reactions to prescription and over the counter drugs
are extremely common in people with HIV. The reactions
involve the skin and may be intensely itchy. They most
commonly occur seven to fourteen days after the initiation of
a new drug and start out as small, flat or slightly raised,
red bumps which coalesce into larger red bumps and may become
completely generalized. The skin eruption may be associated
with fever and malaise. People with HIV are particularly
likely to react to trimethoprim-sulfamethoxazole (TMP-SMX,
Septra, Bactrim) used for the prevention and treatment of
pneumocystis pneumonia, and to penicillins.

In any generalized skin eruption, a drug reaction must be
considered. All those drugs which are either suspected or
unnecessary should be discontinued if possible; over the
counter drugs, herbal remedies, compounds obtained from
buyers' clubs, etc. should be included in this consideration.
Some rashes will resolve while the patient continues on TMP-
SMX, others will require discontinuation. [Note: In many
cases, it is possible to desensitize patients to TMP-SMX, so
that this prophylactic (preventive) treatment for
pneumocystis, and probably also for toxoplasmosis, can be
continued; for more information, see AIDS TREATMENT NEWS,
issues #180, August 6, 1993, and #161, October 16, 1992; or
contact Chris King (see footnote #7, below).]

Dry Skin

Dry skin (also called xerosis or xerotic eczema) is very
common in people with HIV, and is usually associated with
itch. Often the intensity of itch, which may be resistant to
oral antihistamines, seems out of proportion to the visible
dryness. Dry skin is most common on the front of the lower
legs, but may also be seen on the back of the lower legs and
arms, or in a generalized distribution. There may be a fine
scale with occasional red bumps and/or discrete areas of
thickening of the skin secondary to rubbing or scratching.
People with dry skin are at risk for secondary bacterial and
viral infections.

Some patients with dry skin may have a history of allergic
conditions such as asthma, hay fever or atopic dermatitis.
However, many have no such history.(10) Treatment includes
minimizing time in the shower or bath and avoiding very hot
water, using mild soap (for example, Dove) and avoiding
deodorant soaps, and application of moisturizing creams after
bathing and before going to bed. Potent oral antihistamines
such as doxepin may be helpful. Mild topical steroid
ointments (for example, 1% hydrocortisone) can also be used.
Unfortunately, dry skin tends to worsen as HIV-associated
immunosuppression progresses.

Seborrheic Dermatitis and Psoriasis

Seborrheic dermatitis is a common mild skin disorder which
includes dandruff and mild flaking in the eyebrows, behind
the ears and in the area between the nose and the cheeks in
HIV-negative individuals. It is extremely common in people
with HIV, occurring in 30-80% of studied populations. It
often presents very early in the disease, before any other
signs of immunosuppression. It may be mild or quite severe,
involving the eyelashes, inside the ears, central chest,
upper back, under arms, and groin, in addition to the more
common distribution. The rash varies from a very indistinct
light pink slightly raised lesion with very mild, fine, white
scale, to intensely red widespread lesions with profuse,
loose, waxy, yellowish scale. Itch is usually minimal.

Seborrheic dermatitis is a chronic condition with variable
response to treatment. It is believed that an allergic
reaction to the yeast Pityrosporum ovale or Pityrosporum
obicularis may contribute to the development of this
disorder. Treatment includes a topical steroid cream combined
with an anti-fungal cream applied to the affected areas twice
a day. Anti-fungal, tar or selenium shampoos may also be
used. In severe cases, oral anti-fungals may be more
effective. Ultraviolet phototherapy has also been used in
cases which did not respond to other treatments.

Psoriasis is another relatively common flaking skin disorder
with an increased incidence in people with HIV infection.
Approximately 1/3 of patients with psoriasis had it prior to
their HIV infection, while the remaining 2/3 developed it
after they became HIV positive. It is not unusual to see
psoriasis develop in people who previously had seborrheic
dermatitis, and these disorders are often seen as being on a
continuum of severity in people with HIV. Some patients have
a combination of these conditions, referred to as
sebopsoriasis.

When people initially develop psoriasis lesions, which are
pink to red with a silvery scale, they commonly appear on the
knees, elbows and lower back. Initially, they may be very
itchy. As they thicken and become more typical of psoriasis,
the itch usually resolves. Treatment of psoriasis includes
tar preparations, exposure to natural sunlight, ultraviolet
light therapy, and an oral medication called etretinate. Oral
steroids (prednisone) are not used for the treatment of
psoriasis.

The Conant Medical Group has had success with high-dose AZT
for treating severe psoriasis; for more information, contact
Chris King (see footnote #7, below).

Photodermatitis

People with HIV infection appear to be at increased risk for
the development of skin reactions in areas which are exposed
to either sunlight or ultraviolet B (UVB) therapy. Although
the reason is unknown, there are many drugs commonly used by
people with HIV which make them more sensitive to sunlight,
including Bactrim/Septra and non-steroidal anti-
inflammatories (for example ibuprofen, feldene, etc). The
rash is typically itchy and bumpy or scaly and occurs only in
areas exposed to sunlight or light therapy. It may be
confused with seborrheic dermatitis on the face, except the
distribution is reversed: photodermatitis involves the nose
and the area above the eyebrows but spares the crease between
the nose and the cheeks and the eyebrows themselves. There is
also a clear area under the chin.

Phototherapy with UVB has been shown to be helpful in people
with HIV who have psoriasis.(11,12) and eosinophilic
folliculitis.(5) There are theoretical concerns that
phototherapy may be immunosuppressive; it has been shown to
activate HIV replication in the test tube and in mice. In a
study of 6 people over a period of 42 treatments, UVB did not
appear to have a negative effect on the immune system as
measured by lab markers (CD-4 cell count, beta-2-
microglobulin, and p24 antigen) or occurrence of new
opportunistic infection or malignancy.(11) There also remains
some concern that phototherapy may enhance the development of
Kaposi's sarcoma or skin cancers.

A recent study at San Francisco General documented the
development of photosensivity dermatitis in three people with
HIV infection who were being treated with UVB (one for EF,
one for EF and psoriasis, and one for pruritic/itchy
eczematous dermatitis).(6) The authors of this study made the
following recommendations when considering phototherapy in
people with HIV-associated skin disorders: 1) make sure that
the patient does not already have a photodermatitis, 2)
document photosensitizing medications, previous
photosensitivity reactions, and history of KS and skin
cancer, 3) discuss the potential immunosuppressive effects of
phototherapy with the patient, and 4) use the minimal UV dose
required, utilizing additional therapy which enables
reduction in the UVB dose when available (e.g. retinoids in
psoriasis).

Treatment for photodermatitis is usually very successful. It
includes sun avoidance, sunscreens and topical steroids. In
severe cases, oral steroids may be used for a short time.

Systemic Disease

Rarely, people with HIV infection will have itch without any
primary skin lesions.(13) (There may be secondary lesions due
to scratching.) Although occasionally no cause other than the
effects of HIV itself can be found,(14) there are a wide
variety of systemic illnesses associated with itch. The
laboratory evaluation of a specific patient will be directed
by the symptoms, past history, and physical examination and
may include a variety of blood tests, urinalysis, skin
biopsy, radiological/x-ray studies, etc.

Following is a list of systemic illnesses associated with
itch: 1) infectious diseases including hepatitis (especially
hepatitis B), tuberculosis and syphilis; 2) kidney disease;
3) other liver dysfunction, including obstructive biliary
disease; 4) blood disorders including polycythemia vera,
thrombocytosis, chronic lymphocytic leukemia and lymphoma; 5)
other malignancies including breast cancer and occult
malignancy; 6) hormone dysfunction including hypo- or
hyperthyroidism and diabetes mellitus; 7) heart disease
including congestive heart failure and arrhythmias; 8)
central nervous system disorders including tumors,
Huntington's chorea and Parkinson's disease; 9) peripheral
nervous system disorders including peripheral neuropathies;
10) nutritional deficiencies including vitamin B12 and niacin
(pellagra); 11) substance use including alcohol, amphetamines
and cocaine; 12) psychiatric illness including depression,
anxiety, obsessive-compulsive disorder and delusional
parasitosis and 13) medications.

Very infrequently, a person may have a false belief of
infestation, called delusional parasitosis (DP). This is
usually an isolated delusion, but it may be associated with
other mental illness. Sometimes the delusion is shared by a
family member or friend.(15) There is an effective medication
for DP called pimozide (Orap). It has some potentially
serious side effects and is contraindicated in people with
specific heart problems, thus it should be administered under
careful supervision. Relapses of DP do occur when pimozide is
discontinued.

Research into the Mechanisms of Itch and Immunocompromise

Studies are on-going at San Francisco General Hospital and
elsewhere to try to determine the mechanisms involved in
various forms of itchy skin eruptions. An initial study
compared IgE (the allergy related antibody) levels in
patients with eosinophilic folliculitis and those with HIV-
related skin disorders which did not involve itch. This study
documented elevated levels of IgE in patients with clinical
and biopsy proven EF. Current studies are assessing IgE
levels in patients with non-EF associated itch, with the
theory that HIV may be associated with atopy (the tendency to
have allergic-type disorders such as asthma and hay fever).

A second theory, which is also being examined, was spurred by
the observation that an increasing incidence of itch appears
to be associated with declining T-helper cell levels. It is
thought that a change in T-helper cells may occur at around
200, the point at which the incidence of itch appears to
increase, and that the new cells may produce chemicals which
are associated with allergy and itch. Thus, researchers at
San Francisco General Hospital are trying to determine if the
symptom of itch can be used as a marker for disease
progression, in areas where monitoring T-helper cell counts
is neither feasible nor affordable.

Conclusion

Itchy skin can be debilitating in people with HIV infection.
Although it has been tempting in the past to attribute this
symptom to HIV itself, it has recently been recognized by
experienced clinicians and researchers that a specific
diagnosis can often be made. Careful diagnosis is essential
for successful treatment. Patients, primary care physicians
and dermatologists must work together in difficult cases of
itchy skin to establish a diagnosis and devise a reasonable
treatment approach. Multiple therapeutic trials and repeated
visits to the physician may be necessary to find an effective
regimen.

References and Notes

1. Orkin M. Scabies in AIDS. SEMINARS IN DERMATOLOGY. 1993;
volume 12, number 1, pages 9-14.

2. Odom RB and Berger TG. The cutaneous manifestations of
AIDS. CURRENT CONCEPTS (Upjohn). 1990.

3. Orkin M and Maibach HI. Scabies therapy -- 1993. SEMINARS
IN DERMATOLOGY. 1993; volume 12, number 1, pages 22-25.

4. McCalmont TH, Altemus D, Maurer T, and Berger TG.
Eosinophilic folliculitis: the histologic spectrum. In press.

Timothy McCalmont, M.D., dermatopathologist at UCSF, is
willing to consult on cases of suspected EF. He may be
reached by telephone at 415/476-1543 or by fax at 415/476-
4190 to arrange viewing of skin biopsy specimens.

5. Buchness MR, Lim HW, Hatcher VA, Sanchez M, and Soter NA.
Eosinophilic pustular folliculitis in the acquired
immunodeficiency syndrome. Treatment with ultraviolet B
phototherapy. NEW ENGLAND JOURNAL OF MEDICINE. 1988; volume
318, number 18, pages 1183-1186.

6. Thieberg MD and Berger TG. Iatrogenic photodermatitis in
patients with acquired immunodeficiency syndrome. In press.

7. Berger TG, Heon V, King C, Schulze K, and Conant MA.
Itraconazole therapy for HIV-associated eosinophilic
follicultis. In press.

Note that one of the authors of this study, Christopher King,
Assistant Director of Research, Conant Medical Group, has
prepared an extensive written summary of eosinophilic
folliculitis. For more information, you may write to him at
1635 Divisadero St., Suite 601, San Francisco 94115, or fax
him at 415/923-0337. He includes additional treatment
suggestions for patients who do not respond to itraconazole,
including Accutane and/or intermittent low dose systemic
prednisone. Also, an aggressive topical management program is
used.

8. Itraconazole. THE MEDICAL LETTER. 1993; volume 35, number
888, pages 7-9.

9. Berger TG, Obuch ML, and Goldschmidt RH. Dermatologic
manifestations of HIV infection. AMERICAN FAMILY PHYSICIAN.
1990; volume 41, number 6, pages 1729-1742.

10. Cockerell CJ. Seborrheic dermatitis-like and atopic
dermatitis-like eruptions in HIV-infected patients. CLINICS
IN DERMATOLOGY. 1991; volume 9, number 1, pages 49-51.

11. Meola T, Soter NA, Ostreicher R, Sanchez M, and Moy JA.
The safety of UVB phototherapy in patients with HIV
infection. JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY.
1993; volume 29, number 2 part 1, pages 216-220.

12. Pardo RJ, Bogaert MA, Penneys NS, Byrne GE, and Ruiz P.
UVB phototherapy of the pruritic papular eruption of the
acquired immunodeficiency syndrome. JOURNAL OF THE AMERICAN
ACADEMY OF DERMATOLOGY. 1992; volume 26, number 3 part 2,
pages 423-428.

13. Berger TG. Evaluation and treatment of pruritus in the
HIV-infected patient. In Volberding P and Jacobson M. AIDS
CLINICAL REVIEW. 1989; pages 205-220.

14. Hoover WD Jr and Lang PG. Pruritus in HIV infection.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY. 1991;
volume
24, number 6 part 1, pages 1020-1021.

15. Driscoll MS, Rothe MJ, Grant-Kels JM, and Hale MS.
Delusional parasitosis: a dermatologic, psychiatric and
pharmacologic approach. JOURNAL OF THE AMERICAN ACADEMY OF
DERMATOLOGY. 1993; volume 29, number 6, pages 1023-1033.