Mohamed K. Selim, M.D.Richard Dvorak, Ph.D.Qasem A. Alsaleh, M.D.As’ad Al-Hamad Dermatology Center, Al-SabahHospital, Kuwait

Kawasaki Disease and Alopecia Areata:

Coincidence or a True Association?

Abstract: A 10-year-old boy presented with fever,stiff neck, and rash over the legs. During the course ofhis hospital stay, the clinical picture gradually evolved,and he met the criteria for Kawasaki disease (KD) on theseventh day of hospitalization. During this period, healso developed alopecia areata. He was managed withintravenous immunoglobulin, aspirin, and intralesionaltriamcinolone. This is the first case of alopecia areatawith KD in the literature, and it does not appear to be amere coincidence. We discuss the probable mecha-nisms of alopecia areata with KD, an association thathas not been reported before.

Kawasaki disease (KD) is a common febrile immune-related systemic vasculitis of children, first described byTomisaku Kawasaki in 1967. The precise etiology of thedisease remains elusive (1). Immunologic abnormalitieshave been described during the acute phase of KD, al-though thepresenceof a second immunologic disorderorautoimmune disease has been described only occasion-ally in KD (2–5). We describe a 10-year-old boy whopresented with alopecia areata during the acute phase ofKD. This association has not been reported earlier.

CASE REPORT

A 10-year-old boy was referred to us for evaluation offever, rash, and a stiff neck. The fever had been presentfor 3 days and was high-spiking. He had been takingoral amoxicillin capsules for the first 2 days of fever.On the third day of fever, he developed a stiff neckassociated with a rash over the legs, for which he wasreferred to us. There was no cough, headache, vomit-ing, diarrhea, or history of convulsions. He was alertand conscious and had a temperature of 104�F. Vitalsigns were as follows: heart rate 90 beats ⁄minute,respiratory rate 18 per minute, blood pressure

110 ⁄80 mmHg. Perfusion and pulses were normal. Anonpruritic, erythematous, maculopapular rash dis-tributed symmetrically over the bilateral extensor as-pect of legs and over the trunk was noted, withpredominant involvement of the legs. The soles wereinvolved, but the face was spared. There was no pallor,icterus, edema, or lymph node enlargement. Lips andoral mucosa were normal. The chest was clear onauscultation. He had neck rigidity; Kernig’s sign andBrudzinski’s sign were positive. Laboratory investiga-tions were as follows: hemoglobin 11 g ⁄dL, whiteblood cell count 16,500 per mm3 with neutrophilicpredominance, platelet count 40,000 per mm3. Bloodurea, serum creatinine, serum electrolytes, and liverenzymes were normal. Lumbar puncture was done;cerebrospinal fluid (CSF) showed lymphocytic menin-gitis (total leukocytes 40 per mm3, 80% of which werelymphocytes, 20% were neutrophils); CSF glucose was60 mg ⁄dL, and protein level was 28 mg ⁄dL. Gramstain of the fluid did not show bacteria, and culturewas sterile. Blood culture was negative for the growthof any microorganism. A provisional diagnosis ofmeningococcal meningitis (partially treated) was con-sidered. He was treated with intravenous ceftriaxone.

Over the next 5 days, the neck rigidity subsided, butthe fever and rash persisted. On the sixth day of hospi-talization, the patient developed a right cervical non-tender lymph node enlargement measuring 1.5 cm. Lossof hair in round patches was noted on the posterioraspect of the scalp. Periungual desquamation (Fig. 1),erythematous oral and pharyngeal mucosa, andthrombocytosis (platelet count 8, 30,000 per mm3) weredetected on the seventh day of hospitalization. Cheilitiswas present, and the tongue was strawberry colored.There was minimal edema of the palms and soles. There

Address correspondence to Arti Nanda, M.D., DNBE, POBox: 6759, Salmiya 22078, Salmiya, Kuwait, ore-mail: artinanda@hotmail.com.

Figure 1. Periungual desquamation noticed on the 10th dayof illness.

532 Pediatric Dermatology Vol. 29 No. 4 July ⁄August 2012

was no nail pitting. Erythrocyte sedimentation rate(ESR) was 120 mm ⁄hour. Ophthalmologic evaluationincluding slit lamp examination was normal. Throatswab did not show evidence of any microorganismaccording to Gram stain and culture.

The hair loss patch progressed rapidly and becamecomplete over the next 2 days, covering an area 6 cm indiameter (Fig. 2) with exclamation marks, which wereconfirmed using dermoscopy. A final diagnosis of KDwith alopecia areata was made. He was managed withintravenous immunoglobulin (IVIg) and aspirin. Thefever responded promptly within 48 hours of adminis-tration of IVIg and aspirin. Echocardiography wasnormal. Blood glucose and serum T3, T4, and thyroid-stimulating hormone levels were normal. DirectCoomb’s test was negative. Antinuclear antibodies werenegative. Weil Felix test and leptospiral serology werenegative. Intralesional triamcinolone was administeredfor management of alopecia areata.

The patient is under follow-up for the last 6 weeks.Repeated echocardiograms have been normal. Plateletcounts at 2, 4, and 6 weeks of follow-up were 2, 50,000,2, 70, 000, and 3, 40,000 per mm3, respectively. Alopeciaareata has shown partial response with intralesional tri-amcinolone therapy, with patchy regrowth of fine vellushair in the center of the scalp.

DISCUSSION

The diagnosis of KD is based on clinical criteria,including fever for at least 5 days and four or more ofthe following five clinical features—changes in extremi-ties, polymorphous rash, changes in lips and oral cavity,bilateral conjunctival injection, and cervical lymphade-nopathy—and exclusion of alternative diagnoses. Our

patient met the criteria for the diagnosis of KD on theseventh day of hospitalization. Thrombocytosis in thepresence of periungual desquamation (which the patientmanifested later) is highly suggestive of KD (1). Therapid resolution of symptoms after the administration ofaspirin and IVIg is also consistent with the diagnosis ofKD, along with the high platelet count and ESR (6).This impressive response to therapy has been consideredto represent a major test of diagnosis for KD short ofthe development of coronary artery aneurysms (6).Appropriate investigations excluded differential diag-noses such as meningococcemia; systemic lupus erythe-matosus; and staphylococcal, streptococcal, andrickettsial infections. Our patient had some confoundingfeatures also. Initially, meningococcal meningitis wassuspected in view of fever, neck stiffness, and rash.History of prior oral antibiotics and lymphocytic men-ingitis were suggestive of partially treated meningitis.Although aseptic meningitis is seen in one-fourth ofcases of KD (1), neck stiffness is not common. Throm-bocytopenia, which was present in the first week, al-though described in some reports (7), is also an unusualfinding and has been mentioned as a poor prognosticsign. Another notable point is that relatively few peoplewith KD are aged 10 or older.

The etiologyofKDremains an enigma (1).The role ofstaphylococcal and streptococcal superantigens (such astoxic shock syndrome toxin-1) in the etiopathogenesis ofKD has been investigated, and even though a clearimmunologic hypothesis has not been formulated,remarkable activation of the immune system, probablytriggered by these superantigens or other infectiousagents, has been reported (2). Similarly, though theetiopathogenesis of autoimmune diseases is largelyunknown, theprobability that superantigensmight act astriggering factors for immunologic disorders has evokedmuch interest (2). There are only a few reports in theEnglish literature of autoimmune disorders occurring inassociationwithKD. Ina recent studyof 97 childrenwithKD from Italy (2), the prevalence of celiac disease wasfound to be 5.5%, which was significantly higher than incontrols (0.6%). The occurrence of autoimmune hemo-lytic anemia has been mentioned earlier in associationwithKD (3). Other reports include a 5-year-old girl fromCanada (4)whodeveloped systemic lupus erythematosus3.5 years after KD and two African American boys (5)who presented with insulin-dependent diabetes mellitus4 months after being diagnosed with KD. The case de-scribed herein had alopecia areata develop during theacute phase of KD. There are no previous reports ofalopecia areata with KD in the literature. Our case addsto the spectrum of autoimmune disorders described inassociation with KD and may lend support to the

Figure 2. Alopecia areata over the posterior aspect of thescalp.

Brief Reports 533

hypothesis that the reported immune alterations in pa-tients with KD may favor the development of autoim-mune diseases (2).

Diffuse loss of hair has been described in KD (8). Themechanisms proposed for this occurrence include highfever, stress, or severe illness causing all follicles of hair inthe anagen phase to enter the telogen phase andsubsequent shedding of hair, but the pathogenesis ofalopecia areata is different. Alopecia areata is a T-cell-mediated inflammatory disorder affecting the hair folli-cles, with T-lymphocyte infiltration and chemokineexpression being characteristic in involved tissue. Alo-pecia areata is characterized by rapid and complete lossof hair in roundor oval patches on the scalp andonotherbody sites. The association between alopecia areata andautoimmune diseases such as Hashimoto thyroiditis,Addison disease, pernicious anemia, ulcerative colitis,myasthenia gravis, collagen vascular diseases, and viti-ligo is well established, and alopecia areata itself is con-ventionally regarded as an autoimmune disease (9). Ithas been suggested that chemokines such as mono-cyte chemoattractant protein-1 (MCP-1) regulate therecruitment of T lymphocytes around hair follicles (9).Genetic polymorphism in the regulatory regions of theMCP-1 gene have also been associatedwith developmentof coronary artery aneurysms after acute KD (10).Therefore, MCP-1 may be the factor mediating thepathogenesis of KD and alopecia areata in this case,which may explain this association.

To summarize, we present a case of alopecia areataoccurring duringKD in a 10-year-old boy. The temporalassociation between alopecia areata, an autoimmunedisorder, and KD in this case may not be a coincidence.Further studies are needed to delinate probable under-lying links behind this association at the molecular andbiochemical level.

REFERENCES

1. Singh S, Kawasaki T. Kawasaki disease – an Indian per-spective. Indian Pediatr 2009;46:563–571.

2. Stagi S, Simonini G, Ricci L et al. Coeliac disease in pa-tientswithKawasakidisease. Is therea link?Rheumatology(Oxford) 2006;45:847–850.

3. Panzarino V, Estrada J, Benson K et al. Autoimmunehemolytic anemia after Kawasaki disease in a child. Int JHematol 1993;57:259–263.

4. Laxer RM, Cameron BJ, Silverman ED. Occurrence ofKawasaki disease and systemic lupus erythematosus in asingle patient. J Rheumatol 1988;15:515–516.

5. Bhowmick SK, Estrada B, Rettig KR. Insulin-dependentdiabetes mellitus in 2 male African American children afterKawasaki disease. Pediatrics 2002;110:e27.

6. McIntire SC, GreenM. Fever with stiff neck. Arch PediatrAdolesc Med 2001;155:603–606.

7. Hara T, Mizuno Y, Akeda H et al. Thrombocytopenia: acomplication of Kawasaki disease. Eur J Pediatr 1988;147:51–53.

8. Nabavizadeh SH, Safari M, Amin R. Hair loss as a sign ofKawasaki disease. Iran J Allergy Asthma Immunol2006;5:199–200.

9. Tazi-AhniniR,CorkMJ,GawkrodgerDJet al.Roleof theautoimmune regulator (AIRE) gene in alopecia areata:strong association of a potentially functional AIRE poly-morphism with alopecia universalis. Tissue Antigens2002;60:489–495.

10. Jibiki T, Terai M, Shima M et al. Monocyte chemoattr-actant protein-1 gene regulatory region polymorphism andserum levels of monocyte chemoattractant protein-1 inJapanese patients with Kawasaki disease. Arthritis Rheum2001;44:2211–2212.

Sriram Krishnamurthy, M.D.*Laxmisha Chandrashekar, M.D.�Nivedita Mondal, M.D.*Departments of *Pediatrics, �Dermatology, JawaharlalInstitute of Postgraduate Medical Education andResearch, Pondicherry, India

Familial Androgenetic Alopecia in Siblings

with Normal Endocrinological Status

Abstract: Androgenetic alopecia (AGA) is the mostcommon type of hair loss in adults, but it has beenrarely reported in children. We report two cases of AGAin two siblings, aged 6 and 8, whose mother had thesame condition, without any association with other skindiseases or abnormalities in endocrinologic examina-tions.

Androgenetic alopecia (AGA) is the most common typeof hair loss in adults. It clinically appears with hairthinning involving the androgen-dependent areas of thescalp,withmale and female patterns that arewell known.The disease usually starts after puberty, but it has rarelybeen reported in prepubertal children (1–4).

Two sisters, aged 6 and 8, visited our department for a1-year history of hair loss. Onphysical examination, theyboth showed thinning and widening of the central part-ing of the scalp (Fig. 1A,C). A pull test showed greater

Address correspondence to Sriram Krishnamurthy, M.D.,Department of Pediatrics, Jawaharlal Institute of PostgraduateMedical Education and Research (JIPMER), Pondicherry-605006,India, or e-mail: drsriramk@yahoo.com.

534 Pediatric Dermatology Vol. 29 No. 4 July ⁄August 2012