Granuloma Glutaeale Infantum: A Re-emerging Complication of Diaper Dermatitis

Discussion

GGI was first described in 1971 by Tappeiner and Pfleger² as a rare complication of DD with a characteristic presentation consisting of multiple inflammatory papules and nodules. GGI typically occurs in infancy (especially between 4 and 9 months of age).³ Irrespectively of age group, GGI is particularly common in the setting of chronic diarrhea or fecal or urinary incontinence⁴ associated with conditions such as short gut syndrome, inflammatory bowel disease, Hirschsprung disease, or spina bifida. Additionally, GGI occurring in peristomal locations in both children and adults with urostomies or colostomies should be recognized as having a particularly refractory presentation.⁴

The etiology of GGI is not fully understood, but a few contributing factors have been proposed. GGI occurs in the setting of severe irritant contact DD^5,6 related to prolonged occlusion from diapers, resulting in increased exposure to feces and urine. This has not only a direct contributory role but also renders local skin more sensitive to other proposed etiologic factors. These factors include candidiasis,^5,6 foreign material³ such as starch, and topical preparations, especially potent and moderate fluorinated TCS.^3,5 However, Candida and positive polarized examination have not been consistently found in the majority of case reports: an argument against its etiologic role.³ Remarkably, the increased absorption of TCS through inflamed skin of the diaper area can induce alterations in dermal collagen, which may, in turn, be responsible for some of the unique clinical features of GGI. Temporal association between the first GGI descriptions and the widespread use of potent TCS supports their etiologic role. Lastly, the increasing use of cloth reusable diapers has been implicated in the recent re-emergence of papulo-nodular DD complication reports.⁷ Reusable diapers are generally considered to be more ecological and economical, but they are purportedly less absorbent than disposable ones.⁷

The clinical appearance of an asymptomatic eruption of red-purple to red-brown, round to oval, deep, firm nodules with central ulceration is typical. This characteristic, along with the classic distribution over the convexities of the gluteal region, sparing the inguinal folds, points to the clinical diagnosis of GGI.

Nonetheless, when the number of nodules is limited or the dermatitis has atypical clinical features, other conditions must be clinically considered. These include infectious diseases (such as scabetic nodules, genital molluscum contagiosum, and candidiasis) and neoplastic disorders (namely Kaposi sarcoma, mastocytomas, Langerhans cell histiocytosis, and leukemic infiltrates), among others. In addition, other complications of irritant DD may exhibit overlapping clinical features, including extensive and confluent ulcers in Jacquet’s erosive DD and pseudoverrucous papules and nodules.⁸ These complications are deemed to be in the same clinical spectrum of GGI. They probably result from different individual susceptibilities producing polymorphous local presentations as a response to the same pathophysiological mechanisms.⁸

Histologic findings are neither specific nor consistently diagnostic, but their correlation with clinical features allows exclusion of other conditions clinically considered in the differential diagnosis. Histology reveals a nonspecific perivascular dermal infiltrate with lymphocytes, plasma cells, histiocytes, eosinophils, and aggregates of neutrophils forming microabscesses. The overlying epidermis shows prominent acanthosis and parakeratosis.

Removal of the precipitating factors is the key aspect of the treatment.⁹ When this removal is difficult or not possible, such as in the setting of peristomal GGI or chronic medical conditions associated with persistent diarrhea and incontinence, a particular emphasis should be put on local skin care. In these situations, secondary bacterial infections are a common aggravating factor, so swabs for microbiological examination should be obtained routinely specifically from peristomal skin. Prevention of secondary infection and recovery of skin barrier function should be attempted by using gentle antiseptic cleansers and barrier creams, such as zinc oxide or petrolatum-based preparations. Apart from these special settings, specific treatment is generally not needed because the removal of the predisposing factors leads to a spontaneous yet slow-paced resolution.⁹ To minimize morbidity and potential complications arising from this protracted clinical course, many authors have proposed the use of low-potency TCS (such as hydrocortisone).⁹ However, this option is controversial⁵ given the potential etiologic role of corticosteroid preparations in GGI etiology. Additionally, some authors recommend that TCS should not be used in the diaper area, because its application in the locally sensitive and inflamed skin may induce prominent atrophy and other adverse effects, arising from significant local absorption.^5,10

For our patient, we prescribed once-daily application of tacrolimus 0.03% for 8 weeks, resulting in complete resolution of the dermatitis. The clinical remission was maintained for 6 months. Use of topical calcineurin inhibitors (TCIs) for children <2 years of age has not been formally approved; however, large population studies have failed to identify any safety concerns in this population. A recent extensive review concluded that TCIs are safe and effective for the treatment of infants of at least 3 months of age, especially in sensitive skin areas.¹⁰ TCIs do not carry the risk of skin atrophy, impaired barrier function, or enhanced percutaneous absorption, in contrast to TCS. Tacrolimus was well tolerated by our patient and potentially led to a prompt resolution of the initial GGI presentation and its subsequent relapse. We cannot, however, exclude the potential role that may have been played by strict and adequate obedience to the DD general treatment measures that were recommended (although this child’s parents chose to continue using nondisposable diapers). Additionally, we must recognize that a short, tapering course of low-potency TCS may be considered safe and perhaps a good option as a transition therapy to a longer TCI course in patients with protracted disease.

Our patient’s case fits the classic clinical and histologic descriptions of GGI. Additionally, this report emphasizes the emergent etiologic role of reusable diapers in recent reported outbreaks of papulo-nodular DD complications. To the best of our knowledge, this is the first case reporting the use of TCIs in GGI treatment.

DD is a common condition initially presented to pediatricians. The prompt recognition of its complications and appropriate management is crucial for all pediatric physicians. Considering the current increase in GGI reports related to the widespread use of cloth diapers, we aim to alert pediatricians to consider this diagnosis. In particular, physicians should be aware that GGI has a typical presentation that may clinically simulate a granulomatous or a neoplastic disease. Additional studies are required to assess if TCIs might be an option to minimize morbidity and more promptly resolve GGI, without major adverse events.