5 Chapter 34 :: Granuloma Annulare
:: Julie S. Prendiville
AT-A-GLANCE
■ Granuloma annulare is a relatively common
disorder. The exact prevalence is unknown, but it
occurs more often in children and young adults.
■ A localized ring of beaded papules on the
Part 5
extremities is typical; generalized, subcutaneous,
perforating, and patch subtypes also occur.
■ The cause of granuloma annulare is unknown, and
::
the pathogenesis is poorly understood.
■ Pathologic features consist of granulomatous
Lichenoid and Granulomatous Disorders
inflammation in a palisaded or interstitial pattern
associated with varying degrees of connective
tissue degeneration and mucin deposition.
■ Most localized cases resolve spontaneously within
2 years.
Granuloma annulare is a benign self-limited disease
that was first described by Colcott-Fox in 1895 and
Radcliffe-Crocker1 in 1902.
EPIDEMIOLOGY
Granuloma annulare is a relatively common disorder.2
It occurs in all age groups but is rare in infancy.2-4 The
localized annular and subcutaneous forms occur more
frequently in children and young adults. The gen-
eralized or disseminated variant is more common in
adults. Many studies report a female preponderance,2
but some have found a higher frequency in males.5
Granuloma annulare does not favor a particular race
or geographic area.
Most cases of granuloma annulare are sporadic.
Occasional familial cases are described with occur-
rence in twins, siblings, and members of successive
generations.2,6,7 Attempts to identify an associated
human leukocyte antigen subtype have yielded dispa-
rate results in different population groups.
CLINICAL FEATURES
HISTORY
The typical history is of one or more papules with
centrifugal enlargement and central clearing. These
annular lesions are often misdiagnosed as tinea corpo-
ris and treated unsuccessfully with topical antifungal
agents. Subcutaneous nodules may raise suspicion
about malignancy or rheumatoid disease.
Kang_CH034_p0564-0571.indd 564
Granuloma annulare is usually asymptomatic. Mild
pruritus may be present, but painful lesions are rare.
Nodular lesions on the feet may cause discomfort
from footwear. Cosmesis is often a concern for adoles-
cent and adult patients, particularly with generalized
disease.
CUTANEOUS FINDINGS
Clinical variants of granuloma annulare include the
localized, generalized, subcutaneous, perforating, and
patch types. Linear granuloma annulare, a follicular
pustular form, papular umbilicated lesions in children,
and giant plaques have also been described. There is
overlap among the different variants, and more than
one morphologic type may coexist in the same patient.
LOCALIZED TYPE
The most common form of granuloma annulare is an
annular or arcuate lesion. It may be skin colored, ery-
thematous, or violaceous. It usually measures 1 to 5 cm
in diameter.2 The annular margin is firm to palpation
and may be continuous or consist of discrete or coales-
cent papules in a complete or partial circle (Fig. 34-1).
The epidermis is usually normal, but surface markings
may be attenuated over individual papules. Within the
annular ring, the skin may have a violaceous or pig-
mented appearance. Solitary firm papules or nodules
may also be present. Papular lesions on the fingers
may appear umbilicated.
The dorsal hands and feet, ankles, lower limbs, and
wrists are the sites of predilection (see Figs. 34-1 and
34-2). Less commonly, lesions occur at other sites,
including the eyelids. The palms and soles are occa-
sionally involved. Localized annular lesions may coex-
ist with the subcutaneous or patch forms.
GENERALIZED TYPE
The generalized form of granuloma annulare is said to
comprise 8% to 15% of cases.8 The majority of patients
are adults, but it may also be seen in childhood. Unlike
in localized disease, the trunk is frequently involved in
addition to the neck and extremities. The face, scalp,
palms, and soles may also be affected.
Generalized granuloma annulare presents as wide-
spread papules (Fig. 34-3A), some of which coalesce
to form small annular plaques or larger discolored
patches with raised arcuate and serpiginous margins
(see Fig. 34-3B). Lesions may be skin colored, pink,
violaceous, tan, or yellow. An annular or nonannular
30/11/18 2:32 pm

A
B
Figure 34-1 A, Typical annular lesion of granuloma annu-
lare on a finger. B, A larger annular lesion of granuloma
annulare on the dorsum of the hand.
morphology may predominate. A generalized form of
perforating granuloma annulare has also been described.
SUBCUTANEOUS TYPE
The subcutaneous form of granuloma annulare
occurs predominantly in children9,10 but is also
described in adult patients. It is characterized by
Figure 34-2 Localized granuloma annulare with nodule
on the hand of a child.
Kang_CH034_p0564-0571.indd 565
5
A
Chapter 34 :: Granuloma Annulare
B
Figure 34-3 A, Generalized granuloma annulare. Small
papular lesions that are too small to exhibit annular con-
figuration. B, Multiple annular lesions on the lower arm.
firm to hard, usually asymptomatic nodules located
in the deep dermis and subcutaneous tissues. They
may extend to underlying muscle, and nodules on
the scalp and orbit are often adherent to the underly-
ing periosteum.
Individual lesions measure from 6 mm to 3.5 cm
in diameter. They are distributed most often on the
anterior lower legs in a pretibial location. Other
sites of predilection are the ankles, dorsal feet, but-
tocks, and hands. Nodules on the scalp, eyelids, and
orbital rim may present a diagnostic challenge. Sub-
cutaneous granuloma annulare may also be found
on the penis.
PERFORATING TYPE
The perforating type of granuloma annulare is a rare
variant characterized by transepidermal elimination of
the necrobiotic collagen. It may be localized, usually to
the dorsal hands and fingers (Fig. 34-4), or generalized
over the trunk and extremities. It has been described
on the ears, on the scrotum, and within herpes zoster
scars and tattoos. Superficial small papules develop
central umbilication or crusting, and there may be
discharge of a creamy fluid. Lesions heal with atro-
phic or hyperpigmented scars. In one series, 24% of
patients complained of pruritus and 21% of pain. Pap- 565
ular umbilicated granuloma annulare on the hands of
30/11/18 2:33 pm
 5 trauma in 25% of children,2 but this observation has
Part 5
Figure 34-4 Granuloma annulare on the knuckles of a dark-
skinned patient. (Image used with permission from the
Graham Library of Wake Forest Department of Dermatology.)
::
Lichenoid and Granulomatous Disorders
children and a generalized follicular pustular type of
granuloma annulare may be clinical variants.
PATCH TYPE
Macular lesions that present as erythematous, red-
brown, or violaceous patches without an annular rim
are reported in adult women.11 An arcuate dermal ery-
thema is also observed.
NONCUTANEOUS FINDINGS
Most patients with granuloma annulare are healthy and
have no other abnormal physical findings. Arthralgia
is reported in association with painful lesions on the
hands.12 Granuloma annulare–like skin lesions and joint
disease characterize a multisystem disorder described
as interstitial granulomatous dermatitis with arthritis.13
Oral involvement has been observed in HIV-associated
disease.14
ETIOLOGY AND
PATHOGENESIS
The etiology of granuloma annulare is unknown, and
the pathogenesis is poorly understood. Most cases
occur in otherwise healthy children. A variety of pre-
disposing events and associated systemic diseases is
reported, but their significance is unclear. It is possible
that granuloma annulare represents a phenotypic reac-
tion pattern with many different initiating factors.
PREDISPOSING EVENTS
Nonspecific mild trauma is considered a possible trig-
gering factor because of the frequent location of lesions
566 on the distal extremities of children. An early study of
subcutaneous granuloma annulare found a history of
Kang_CH034_p0564-0571.indd 566
not been replicated. Trauma is also a suspected factor
in auricular lesions. Granuloma annulare has occurred
after a bee sting, a cat bite, and an octopus bite, and
insect bite reactions have also been implicated.2 There
is a report of perforating granuloma annulare in long-
standing tattoos. Widespread lesions have developed
after waxing-induced pseudofolliculitis and erythema
multiforme minor and in association with systemic
sarcoidosis.2,15 Severe uveitis without other evidence of
sarcoidosis has occurred in a few patients with granu-
loma annulare.16-18
INFECTIONS AND IMMUNIZATIONS
There are several reports of the development of granu-
loma annulare within herpes zoster scars, sometimes
many years after the active infection. It is also described
after chickenpox. Generalized, localized, and perforat-
ing forms of granuloma annulare may occur in asso-
ciation with HIV infection. Adenovirus was isolated
from a lesion in one HIV-positive patient. Epstein-Barr
virus was excluded as a causative agent in these cases.
However, in other instances, generalized granuloma
annulare has been linked to viral infections, including
Epstein-Barr virus infection, chronic hepatitis B, and
hepatitis C. Vaccinations for tetanus, diphtheria toxoid,
and hepatitis B vaccination have been implicated as trig-
gering factors, although vaccination sites were spared in
one case of generalized granuloma annulare.19
Lesions compatible with granuloma annulare may
occur in patients with active tuberculosis. There are
also reports of granuloma annulare after tuberculin
skin tests and bacille Calmette–Guérin immunization.
Evidence of Borrelia burgdorferi infection was detected
in two reports, but this association was not confirmed
in a serologic study. A case in which chronic relapsing
granuloma annulare flared during scabies infestation
was attributed to the Koebner phenomenon.20
SUN EXPOSURE
Granuloma annulare with a predilection for sun-
exposed areas and seasonal recurrence has been
described. Photosensitive granuloma annulare has
been observed in patients with HIV infection.14 Gener-
alized disease after psoralen plus ultraviolet A (UVA)
light therapy is reported, but it is of note that photo-
therapy and PUVA phototherapy have been used to
treat generalized granuloma annulare.21-23
Actinic granuloma, also known as annular elastolytic
giant cell granuloma, develops on photodamaged skin
and is believed to represent a granulomatous reac-
tion to actinic elastosis.24 Its relationship to granuloma
annulare is debated.
DRUGS
Granuloma annulare–like drug reactions are reported
for gold therapy and treatment with allopurinol,
diclofenac, quinidine, intranasal calcitonin, topiramate,
30/11/18 2:33 pm
 amlodipine, and thalidomide.25 There are also reports
of an association with adalimumab, infliximab, etaner-
cept, efalizumab, and vemurafinib.22,23,25
An interstitial granulomatous drug reaction linked
to the use of angiotensin-converting enzyme inhibi-
tors, calcium channel blockers, and other medications
is considered a distinct entity but may mimic granu-
loma annulare.26,27
PATHOGENIC MECHANISMS
The pathogenic mechanisms that result in foci of
altered connective tissue surrounded by a granuloma-
tous inflammatory infiltrate are not understood. Pro-
posed mechanisms include (1) a primary degenerative
process of connective tissue initiating granulomatous
inflammation, (2) a lymphocyte-mediated immune
reaction resulting in macrophage activation and
cytokine-mediated degradation of connective tissue,
and (3) a subtle vasculitis or other microangiopathy
leading to tissue injury.28-30
SYSTEMIC DISORDERS AND
GRANULOMA ANNULARE
DIABETES MELLITUS AND
THYROID DISEASE
Development of granuloma annulare in patients with
diabetes mellitus is extensively documented. Whether
this is a true relationship has long been debated. The
link is primarily with type 1 insulin-dependent diabe-
tes, but cases are also reported with type 2 non–insulin-
dependent disease. Localized and generalized as well
as subcutaneous nodular and perforating forms of
granuloma annulare have been observed. Granuloma
annulare rarely predates the onset of diabetes. The his-
topathologic similarity between granuloma annulare
and necrobiosis lipoidica diabeticorum and the coexis-
tence of both conditions in occasional diabetic patients
suggest a true association. However, most patients
with granuloma annulare do not have diabetes melli-
tus. Studies attempting to establish a causal correlation
have yielded conflicting results.22
Granuloma annulare has also occurred in a number
of patients with thyroiditis, hypothyroidism, and thy-
roid adenoma.22
MALIGNANCY
An association between granuloma annulare and
malignancy in adult patients is reported primarily
with Hodgkin and non-Hodgkin lymphoma, including
mycosis fungoides, Lennert lymphoma, B-cell disease,
T-cell leukemia and lymphoma, and angioblastic T-cell
lymphoma. It is reported less commonly with myeloid
Kang_CH034_p0564-0571.indd 567
leukemias and with solid tumors, particularly of the
breast. The skin lesions of cutaneous lymphoma and
5
other hematologic malignancies can mimic granuloma
annulare both clinically and histopathologically. It
may be difficult to distinguish whether they represent
true granuloma annulare with atypical lymphocytes
or cutaneous lymphoma obscured by a granulomatous
infiltrate.31,32
DYSLIPIDEMIA
An increased prevalence of dyslipidemia has been
reported in patients with granuloma annulare.32 This
was more commonly found in generalized granu-
Chapter 34 :: Granuloma Annulare
loma annulare, particularly in cases with an annular
morphology.
LABORATORY TESTS
A diagnosis of localized granuloma annulare is made
on clinical examination, and further evaluation is
rarely indicated. Biopsy to obtain a specimen for his-
topathologic examination is necessary when the pre-
sentation is atypical, when lesions are symptomatic,
and when the diagnosis is otherwise in doubt. His-
topathologic analysis may be required to confirm a
diagnosis of generalized granuloma annulare or sub-
cutaneous nodular disease on the head and orbital
region.
HISTOPATHOLOGIC
FINDINGS
The diagnosis is best made at low magnification.
Changes are usually observed in the upper and middle
dermis, although any part of the dermis or subcutis can
be involved. The characteristic histopathologic find-
ing is a lymphohistiocytic granuloma associated with
varying degrees of connective tissue degeneration and
mucin deposition. The inflammatory infiltrate may
have a palisaded or interstitial pattern or a mixture of
both patterns.33-35 Occasionally, a sarcoid-like pattern
with large epithelioid histiocytes is seen.
The typical appearance is of single or multiple foci
of inflammation with a central core of altered collagen
(necrobiosis) surrounded by a wall of palisaded his-
tiocytes (Fig. 34-5). The necrobiotic centers are usually
oval, slightly basophilic, devoid of nuclei, and marked
by a loss of definition of the collagen bundles and
diminished or absent elastic tissue fibers. Stains for
mucin and lipid often give positive results.36
An interstitial, nonpalisaded pattern of inflamma-
tion with histiocytes infiltrating among fragmented
collagen bundles may be predominant, particularly in
the generalized form. This interstitial pattern is also
observed in the absence of apparent connective tissue
change. Stains for mucin may be helpful in detecting 567
connective tissue alteration within the infiltrate.
30/11/18 2:33 pm
 5
Part 5
Figure 34-5 Palisading granulomatous inflammation sur-
rounding degenerating collagen within the dermis.
::
(Hematoxylin and eosin stain, ×200.) (Used with permis-
sion from Dr. Richard Crawford.)
Lichenoid and Granulomatous Disorders
Lymphocytes are admixed with histiocytes in the
granuloma and in a perivascular distribution. Mul-
tinucleated giant cells may be present but are not as
numerous as in actinic granuloma.37 Neutrophils and
eosinophils are occasionally seen, but plasma cells
are rare. Evidence of vascular reactivity includes vari-
able endothelial cell swelling, red cell extravasation,
fibrin, leukocytoclasis, and neutrophilic infiltration in
blood vessel walls. When leukocytoclastic vasculitis or
nuclear debris is a prominent finding, a diagnosis of
palisaded neutrophilic and granulomatous dermatitis
of immune complex disease should be considered.38
In subcutaneous granuloma annulare (Fig. 34-6), the
foci of necrobiosis are larger and lie within the deep
dermis and subcutaneous fat. They may be distin-
guished from rheumatoid nodules by the presence of
mucin in the necrobiotic zone. Central ulceration and
communication between the area of necrobiosis and
the surface are characteristic of perforating granuloma
annulare (Fig. 34-7). Examination of serial sections
may be necessary to demonstrate the necrobiotic plug.
An interstitial pattern of inflammation with diffuse
necrobiosis is reported in the patch type of granuloma
Figure 34-6 Subcutaneous granuloma annulare pathol-
568 ogy. (Used with permission from the Graham Library of
Wake Forest Department of Dermatology.)
Kang_CH034_p0564-0571.indd 568
A
B
Figure 34-7 A and B, Histopathology of perforating gran-
uloma annulare. (Used with permission from the Graham
Library of Wake Forest Department of Dermatology.)
annulare. Palisaded granulomas have also been
observed in macular lesions.
Immunofluorescence testing may show deposition
of fibrin, immunoglobulin (Ig) M, and C3 as a vari-
able finding around vessel walls or at the basement
membrane zone; IgM cytoid bodies are also reported.39
Immunohistochemistry may be useful to confirm the
histiocytic nature of equivocal disease. Ultrastructural
changes in the connective tissue and capillaries have
been described.40
SPECIAL TESTS
A diagnosis of granuloma annulare is made clinically
or by skin biopsy. Special investigations are usually
not necessary. Further evaluation to rule out systemic
disease such as infection, sarcoidosis, or malignancy
may be required in atypical cases of granuloma annu-
lare. Investigation for endocrine disease is indicated if
the patient has signs or symptoms of diabetes or thy-
roid dysfunction. Lipid studies may be considered in
the evaluation of generalized granuloma annulare.32
Imaging studies may be performed in subcutaneous
granuloma annulare when the clinical features are not
recognized or when the presentation is atypical with
rapid enlargement or pain. Radiographs show a non-
specific soft tissue mass without calcification or bone
involvement. Ultrasonographic examination reveals
30/11/18 2:33 pm
 TABLE 34-1
a hypoechoic area in the subcutaneous tissues.41,42
Magnetic resonance imaging shows a mass with indis-
5
Differential Diagnosis of Granuloma tinct margins, isointense or slightly hyperintense to
Annulare muscle with T1-weighted images and with a hetero-
geneous but predominantly high signal intensity on
Annular Type
T2-weighted images.41,43
Consider
■ Tinea corporis
■ Subacute cutaneous lupus erythematosus
■ Neonatal lupus erythematosus
DIFFERENTIAL DIAGNOSIS
■ Annular lichen planus See Table 34-1.
■ Acute febrile neutrophilic dermatosis
■ Erythema chronicum migrans
■ Actinic granuloma/annular elastolytic giant cell granuloma
■ Necrobiosis lipoidica diabeticorum
TREATMENT

Chapter 34 :: Granuloma Annulare

Rule Out The usual treatment options include awaiting spon-
■ Infections (eg, tuberculosis, atypical mycobacteria, syphilis) taneous resolution, topical steroids, and intralesional
■ Interstitial granulomatous dermatitis with arthritis steroids. These and various other therapies of anec-
■ Interstitial granulomatous drug reaction dotal benefit are summarized in Table 34-2. Most
■ Annular sarcoidosis
■ Lymphoma
Generalized Type TABLE 34-2
Consider Treatment Options for Granuloma Annulare
■ Lichen planus
■ Lichen nitidus ■ Await spontaneous resolution
■ Molluscum contagiosum ■ Apply topical corticosteroid with or without occlusion
■ Administer intralesional triamcinolone 2.5 mg/mL
Rule Out
■ Lichenoid and granulomatous dermatitis of acquired Anecdotal Reports of Benefit
immunodeficiency syndrome ■ Topical
■ Infections (eg, tuberculosis, atypical mycobacteria, syphilis) ■ Tacrolimus 0.1% ointment
■ Sarcoidosis ■ Pimecrolimus cream
■ Blau syndrome (familial granulomatous arthritis, skin eruption, and ■ Imiquimod 5% creama
uveitis) ■ Intralesional
■ Interstitial granulomatous drug reaction ■ Interferon-γ
■ Lymphoma ■ Interferon-β
■ Sterile water or saline
Subcutaneous Type
■ Systemic
Consider ■ Antimalarials
■ Erythema nodosum ■ Retinoids
■ Dermoid cyst ■ Antibioticsb
■ Rheumatoid nodules ■ Corticosteroids
Rule Out ■ Cyclosporine
■ Epithelioid sarcoma ■ Zileuton with vitamin E
■ Benign or other malignant tumors ■ Fumaric acid esters
■ Deep infections ■ Pentoxifylline
■ Hydroxyurea, chlorambucil, niacinamide, potassium iodide,
Perforating Type
dapsone
Consider ■ Etanerceptc
■ Molluscum contagiosum ■ Infliximabc
■ Insect bites ■ Efalizumabc
■ Pityriasis lichenoides ■ Adalimumabc
■ Perforating collagenosis and other perforating disorders ■ Other
■ Foreign body granuloma ■ Phototherapyd
■ Papulonecrotic tuberculid ■ Photodynamic therapy
■ Palisaded neutrophilic and granulomatous dermatitis of immune ■ Fractional photothermolysis
complex disease Skin biopsy
Patch Type ■ Cryotherapy
■ Pulsed dye, Excimer, Nd:YAG or CO2 laser
Consider
■ Morphea a
Application of 5% imiquimod cream has been reported to worsen granu-
■ Erythema annulare centrifugum loma annulare in a child.
■ Parapsoriasis b
Triple antibiotic regimen (rifampicin, ofloxacin, minocycline), doxycycline,
Rule Out antituberculosis therapy.
■ Lymphoma Development of granuloma annulare has been reported during therapy
c

with etanercept, infliximab, and adalimumab.

d
Narrowband ultraviolet B, ultraviolet A1, psoralen plus ultraviolet A. 569
Nd:YAG, neodymium-doped yttrium aluminum garnet.

Kang_CH034_p0564-0571.indd 569 30/11/18 2:33 pm

 5 treatment recommendations are based on single case
reports and small cases series, and there are no con-
trolled studies.21-23,44-47
CLINICAL COURSE AND
PROGNOSIS
Most cases of localized granuloma annulare resolve
spontaneously without sequelae. Lesions may clear
within a few weeks or persist for several years. The
majority disappear within 2 years. Recurrent lesions
may develop months or even years later, frequently at
the same site. Generalized granuloma annulare often
Part 5
runs a more protracted course. Perforating granuloma
annulare results in scarring. There are a number of
reports of anetoderma or middermal elastolysis fol-
::
lowing generalized granuloma annulare and annular
Lichenoid and Granulomatous Disorders
elastolytic giant cell granuloma.48,49 One case of gener-
alized granuloma annulare in a photosensitive distri-
bution healed with scarring and milia formation.50
REFERENCES
1. Radcliffe Crocker H. Granuloma annulare. Br J Dermatol.
1902;14:1.
2. Muhlbauer JE. Granuloma annulare. J Am Acad Dermatol.
1980;3:217.
3. De Aloe G, Risulo M, Sbano P, et al. Congenital subcutane-
ous granuloma annulare. Pediatr Dermatol. 2005;22:234.
4. Choi J-C, Bae J-Y, Cho S, et al. Generalized perforating
granuloma annulare in an infant. Pediatr Dermatol.
2003;20:2.
5. Martinon-Torres F, Martinon-Sanchez JM, Martinon-
Sanchez F. Localized granuloma annulare in children:
a review of 42 cases. Eur J Paediatr. 1999;158:866.
6. Friedman SJ, Winkelmann RK. Familial granuloma
annulare. J Am Acad Dermatol. 1987;16:600.
7. Abrusci V, Weiss E, Planas G. Familial perforating gran-
uloma annulare. Int J Dermatol. 1988;27:126.
8. Dabski K, Winkelmann RK. Generalized granuloma
annulare: clinical and laboratory findings in 100 patients.
J Am Acad Dermatol. 1989;20:39.
9. Grogg KL, Nascimento AG. Subcutaneous granuloma
annulare in childhood: clinicopathologic features in
34 cases. Pediatrics. 2001;107:e42.
10. Felner EI, Steinberg JB, Weinberg AG. Subcutaneous
granuloma annulare: a review of 47 cases. Pediatrics.
1997;100:965.
11. Mutasim DF, Bridges AG. Patch granuloma annu-
lare: clinicopathologic study of 6 patients. J Am Acad
Dermatol. 2000;42:417.
12. Brey NV, Malone J, Callen JP. Acute-onset, painful acral
granuloma annulare. Arch Dermatol. 2006;142:49.
13. Long D, Thiboutot DM, Majeski JT, et al. Interstitial
granulomatous dermatitis with arthritis. J Am Acad
Dermatol. 1996;34:957.
14. Cohen PR. Granuloma annulare: a mucocutaneous
condition in human immunodeficiency virus-infected
patients. Arch Dermatol. 1999;135:1404.
15. Ehrich EW, McGuire JL, Kim YH. Association of granu-
570 loma annulare with sarcoidosis. Arch Dermatol. 1992;
128:855.
Kang_CH034_p0564-0571.indd 570
16. van Kooij B, van Dijk MC, de Boer J, et al. Is granuloma
annulare related to intermediate uveitis with retinal
vasculitis? Br J Ophthalmol. 2003;87:763.
17. Brey NV, Purkiss TJ, Sehgal A, et al. Association of
inflammatory eye disease with granuloma annulare?
Arch Dermatol. 2008;144:803.
18. Arekapudi S, Whitfield K, Morrison D. Panuveitis asso-
ciated with granuloma annulare in a child. J Pediatr
Ophthalmol Strabismus. 2009;46:45.
19. Huilgol SC, Liddell K, Black MM. Generalized granuloma
annulare sparing vaccination sites. Clin Exp Dermatol.
1995;20:51.
20. Wilsmann-Theis D, Wenzel J, Gerdsen R, et al. Granu-
loma annulare induced by scabies. Acta Derm Venereol.
2003;83:318.
21. Pavlovsky M, Samuelov L, Sprecher E, et al. NB-UVB
phototherapy for generalized granuloma annulare.
Dermatol Ther. 2016; 29:152.
22. Thornsberry LA, English JC. Etiology, diagnosis, and
therapeutic management of granuloma annulare: an
update. Am J Clin Dermatol. 2013;14:279.
23. Keimig EL. Granuloma annulare. Dermatol Clin. 2015;
33(3):315-29.
24. O’Brien JP, Regan W. Actinically degenerate elastic tis-
sue is the likely antigenic basis of actinic granuloma of
the skin and of temporal arteritis. J Am Acad Dermatol.
1999;40:214.
25. Lee SB, Weide B, Ugurel S, et al. Vemurafenib-
induced granuloma annulare. J Dtsch Dermatol Ges.
2016;14:305.
26. Magro CM, Crowson AN, Schapiro BL. The interstitial
granulomatous drug reaction. A distinctive clinical
and pathological entity. J Cutan Pathol. 1998;25:72.
27. Perrin C, Lacour J-P, Castanet J, et al. Interstitial granu-
lomatous drug reaction with a histological pattern of
interstitial granulomatous dermatitis. Am J Dermato-
pathol. 2001;23:295.
28. Dahl MV. Speculations on the pathogenesis of granu-
loma annulare. Australas J Dermatol. 1985;26:49.
29. Mempel M, Musette P, Flaguel B, et al. T-cell receptor
repertoire and cytokine pattern in granuloma annu-
lare: defining a particular type of cutaneous granulo-
matous inflammation. J Invest Dermatol. 2002;118:957.
30. Fayyazi A, Schweyer S, Eichmeyer B, et al. Expression
of IFNγ, coexpression of TNFα and matrix metallopro-
teinases and apoptosis of T lymphocytes and macro-
phages in granuloma annulare. Arch Dermatol Res.
2000;292:384.
31. Jouary T, Beylot-Barry M, Bergier B, et al. Mycosis fun-
goides mimicking granuloma annulare. Br J Dermatol.
2002;146:1102.
32. Wu H, Barusevicius A, Lessin SR. Granuloma annu-
lare with mycosis fungoides-like distribution and
palisaded granulomas of CD-68-positive histiocytes.
J Am Acad Dermatol. 2004;51:39.
33. Friedmann-Birnbaum R, Weltfriend S, Munichor M,
et al. A comparative histopathologic study of general-
ized and localized granuloma annulare. Am J Dermato-
pathol. 1989;11:144.
34. Stefanaki K, Tsivitanidou-Kakourou T, Stefanaki C, et al.
Histological and immunohistochemical study of gran-
uloma annulare and subcutaneous granuloma annu-
lare in children. J Cutan Pathol. 2007;34:392.
35. Dabski K, Winkelmann RK. Generalized granuloma
annulare: histopathology and immunopathology. A
systematic review of 100 cases and comparison with
localized granuloma annulare. J Am Acad Dermatol.
1989;20:28.
30/11/18 2:33 pm
 36. Schulman JM, LeBoit P. Adipophilin expression in
necrobiosis lipoidica, granuloma annulare, and sarcoid-
osis. Am J Dermatopathol. 2015;37:203.
37. Al-Hoqail IA, Al-Ghamdi AM, Martinka M, et al.
Actinic granuloma is a unique and distinct entity: a
comparative study with granuloma annulare. Am J
Dermatopathol. 2002;24:209.
38. Chu P. Connolly MK, LeBoit PE. The histopathologic
spectrum of palisaded neutrophilic and granulomatous
dermatitis in patients with collagen vascular disease.
Arch Dermatol. 1994;130:1278.
39. Stefanaki K, Tsivitanidou Kakourou T, Sefananaki C,
et al. Histological and immunohistochemical study of
granuloma annulare and subcutaneous granuloma
annulare in children. J Cutan Pathol. 2007;34:392.
40. Hanna WM, Moreno-Merlo F, Andrighetti L. Granuloma
annulare: an elastic tissue disease? Case report and
literature review. Ultrastructural Pathol. 1999;23:33.
41. Chung S, Frush DP, Prose NP, et al. Subcutaneous gran-
uloma annulare: MR imaging features in six children
and literature review. Radiology. 1999;210:845.
42. Stenzel M, Voss U, Mutze S, et al. A pretibial lump in a
toddler—sonographic findings in subcutaneous gran-
uloma annulare. Ultraschall Med. 2010;31:68.
43. Navarro OM, Laffan EE, Ngan B-Y. Pediatric soft-tissue
tumors and pseudotumors: MR imaging features with
pathologic correlation. Radiographics. 2009;29:887.
Kang_CH034_p0564-0571.indd 571
44. Lukacs J, Schliemann S, Elsner P. Treatment of general-
ized granuloma annulare—a systematic review. J Eur
5
Acad Dermatol Venereol. 2015;29:1467.
45. Min MS, Lebwohl M. Treatment of recalcitrant granu-
loma annulare with adalimumab. J Am Acad Dermatol.
2016;74:127.
46. Simpson B, Foster S, Ku JH, et al. Triple antibiotic com-
bination therapy may improve but not resolve granu-
loma annulare. Dermatol Ther. 2014;27:343.
47. Verne SH, Kennedy J, Falto-Aizpurua LA, et al. Laser
treatment of granuloma annulare: a review. Int J
Dermatol. 2016;55:376.
48. Kang HS, Paek JO, Lee MW, et al. Anetoderma devel-
oping in generalized granuloma annulare in an infant.
Ann Dermatol. 2014;26:283.
49. Sanyal S, Hejmadi R, Taibjee SM. Granuloma annulare
Chapter 34 :: Granuloma Annulare
resolving with features of mid-dermal elastolysis. Clin
Exp Dermatol. 2009;34:e1017.
50. Gass JK, Todd PM, Rytina E. Generalized granuloma
annulare in a photosensitive distribution resolving
with scarring and milia formation. Clin Exp Dermatol.
2009;34:e53.
571
30/11/18 2:33 pm