Loretta S Davis, MD

A healthy 15-year-old girl presents for evaluation of itchy, painful bumps on her toes that developed 3 weeks earlier. The bumps become more numerous and bothersome when she is outdoors sledding and skiing.

Pernio, or chilblains, is a chronic condition classically presenting as red-to-purple, edematous lesions of variable sizes on acral skin, typically fingers and toes. Lesions are commonly painful and pruritic, and they may progress to blisters and ulcers predisposing to infection. Symptoms result from abnormal vasoconstriction in response to physiologic stress, such as cold temperatures and hypoxemia.

The course may be acute, initiating as quickly as 24 hours following insult and improving within 3 weeks, or chronic, persisting or recurring over weeks to months despite lack of repeated insults.

 One-third of patients show at least 1 laboratory abnormality that may raise concern for underlying hematologic or rheumatologic disease.

 Patients with secondary perniosis due to such conditions are more likely to present with chronic symptoms.

The differential diagnosis for pernio includes leukocytoclastic vasculitis, Henoch-Schonlein Purpura, and hand-foot-mouth disease. Chilblains lupus erythematosus is an uncommon disorder that presents with both the characteristic discoid papules of cutaneous lupus erythematosus as well as the lesions of pernio.

 A complete history that includes recent illnesses, medications, triggers, and other involved organs is vital to the diagnosis of pernio.

Though not required, skin biopsy may be utilized when the diagnosis is unclear. Supporting histopathology shows papillary dermal edema with lymphocytic infiltrate surrounding blood vessels and adnexal structures.

 Laboratory workup includes a complete blood count (CBC) and antinuclear antibody (ANA) titers to rule out underlying hematologic or rheumatologic abnormalities.

First-line management for pernio involves keeping extremities warm and dry. Medium-to-high potency topical corticosteroids are thought to be beneficial in clinical practice, however, no large, randomized trials have investigated their effectiveness. The vasodilatory calcium channel blocker nifedipine used for 6 weeks may alleviate symptoms, although evidence for its efficacy is conflicting.

Review of systems for this patient included frequent discoloration and loss of sensation in the hands and feet during winter months. She denied foot trauma, lesions elsewhere on her body, recent infection, new medications, abdominal pain, chills, and joint pains.

Examination revealed erythematous-to-violaceous, edematous papules and small plaques on the dorsal feet with greatest density on the toes (Figure 1). Laboratory studies revealed positive ANA (1:320) with speckled pattern and normal CBC, erythrocyte sedimentation rate, C-reactive protein, C3, C4, anti-Smith, anti-double-stranded DNA, anti-Ro, and anti-La antibodies. Biopsy showed mild subepidermal edema with brisk perivascular and periadnexal lymphocytic infiltrate (Figure 2).

The patient was diagnosed with pernio based on clinical history and biopsy results. Despite her ANA results, she did not meet criteria for any form of lupus erythematosus. She was counseled on keeping her hands and feet dry and wearing insulated gloves and footwear.

Two months later, her symptoms improved with onset of warmer weather. Two years later, despite continued conservative management, her symptoms recurred. Clobetasol ointment twice daily for no more than 2 consecutive weeks was prescribed. The lesions cleared within 6 months.

1. Simon TD, Soep JB, Hollister JR. Pernio in pediatrics. 

2. Lutz V, Cribier B, Lipsker D. Chilblains and antiphospholipid antibodies: report of four cases and review of the literature. 

3. Viguier M, Pinquier L, Cavalier-balloy B, et al. Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erthyromatosus. 

4. Weston WL, Morelli JG. Childhood pernio and cryoproteins. 

5. Tacki Z, Vahaboglu G, Eksioglu H. Epidemiological patterns of perniosis, and its association with systemic disorder. 

6. Arias-Santiago SA, GirÃ³n-Prieto MS, Callejas-Rubio JL, FernÃ¡ndez-Pugnaire MA, Ortego-Centeno N. Lupus pernio or chilblain lupus? Two different entities. 

7. Boada A, Bielsa I, FernÃ¡ndez-Figueras MT, FerrÃ¡ndiz C. Perniosis: clinical and histopathological analysis. 

8. Rustin MH, Newton JA, Smith NP, Dowd PM. The treatment of chilblains with nifedpine: the results of a pilot study, a double-blind placebo-controlled randomized study and a long-term open trial. 

9. Patra AK, Das AL, Ramadasan P. Diltiazem vs. nifedipine in chilblains: a clinical trial. 

10. Souwer IH, Bor JH, Smits P, Lagro-Janssen AL. Nifedipine vs placebo for treatment of chronic chilblains: a randomized controlled trial. 

Articles

A healthy 15-year-old girl presents for evaluation of itchy, painful bumps on her toes that developed 3 weeks earlier. The bumps become more numerous and bothersome when she is outdoors sledding and skiing. What's the diagnosis?

Teenager bothered by painful bumps on toes

A healthy, afebrile, 12-month-old girl presents for evaluation with an asymptomatic nodule on her left cheek that has been present for 3 weeks (Figure 1). She was initially seen by her pediatrician, diagnosed with cellulitis, and prescribed an oral antibiotic, which was not administered by her parents.

Cold panniculitis is a phenomenon that occurs primarily in infants and young children due to a higher proportion of saturated fats in subcutaneous fat compared with older children and adults.

 Saturated fats become solid with cold exposure at a relatively higher temperature than unsaturated fats, leading to the potential for fat crystallization and adipocyte damage with short exposures to cold.

Development of cold panniculitis after exposure to popsicles and cold environments has been reported particularly in young children.

 Additionally, there have been reports of cold panniculitis as a complication of ice pack application to the face and as a vagal maneuver to treat supraventricular tachycardia in newborns.

 Red, indurated plaques typically develop 24 to 72 hours after exposure, frequently occurring on the cheeks or chin due to a higher amount of subcutaneous fat in these areas.

Whereas a clinical diagnosis can be made by physical examination in the setting of an appropriate history, histopathology is confirmatory but usually not necessary. A lobular panniculitis with a lymphocytic and histiocytic inflammatory infiltrate is present at the junction of the dermis and subcutaneous fat.

Included in the differential diagnosis of cold panniculitis are the other panniculitides seen in the pediatric population. These include subcutaneous fat necrosis of the newborn (SCFN), poststeroid panniculitis, and sclerema neonatorum.

 Subcutaneous fat necrosis of the newborn appears in full-term infants and may be associated with perinatal complications. Erythematous to violaceous indurated plaques or subcutaneous nodules appear within days to weeks of birth. Much of the body can be involved, but the anterior trunk is classically spared.

 Although benign, SCFN should be differentiated from cold panniculitis due to the potential for metabolic derangements, specifically hypercalcemia. The possibility of such complications necessitates clinical monitoring of patients with SCFN.

Post-steroid panniculitis characteristically presents in children who are on high doses of systemic corticosteroids followed by rapid withdrawal.

 Erythematous subcutaneous nodules develop within several days of steroid cessation, most commonly on the cheeks, again attributed to the high concentration of fat in this area as occurs with steroid therapy. The lesions are typically asymptomatic, but they can ulcerate and scar.

In the absence of a characteristic history for cold panniculitis, punch biopsy can be performed to support the diagnosis and rule out other conditions. Subcutaneous fat necrosis of the newborn is characterized by a radial pattern of needle-shaped crystals on histology.

 Unlike cold panniculitis wherein infiltrates are limited to the upper subcutis, inflammation in SCFN involves the entire subcutaneous fat layer. Post-steroid panniculitis can appear identical to SCFN on biopsy but is easily distinguished with clinical correlation of high dose steroid use.

Sclerema neonatorum is a panniculitis most commonly seen in premature infants with infection or heart disease. Diffuse woody induration starts on the buttocks and thighs, with rapid extension to include other areas of the body. Feeding and respiration can be impaired if involvement is extensive enough to limit movement. Despite the ill appearance of the infant, histology may reveal only mild changes with little to no inflammation.

 Infectious cellulitis may also be considered in the differential diagnosis in the setting of a febrile and ill-appearing infant.

No treatment is required for cold panniculitis. In the setting of an appropriate history and characteristic morphology, the patient can be monitored for improvement. The lesions typically progress from red to purple in color, with gradual improvement of induration. Complete resolution is expected in a period of weeks to months.

On examination, the child was playful and afebrile. Upon further questioning, mother reported that the child lived in Alaska and spent time outside when at daycare.

At the time of this patient’s evaluation, 3 weeks after onset of the rash, the mother reported that the child’s lesion was spontaneously improving. Examination revealed a well-demarcated purple to red plaque, with greatly reduced erythema compared with the initial lesion (Figure 2). The mother was reassured of the benign nature of cold panniculitis and the expectation for full resolution. Ongoing protection from extreme cold exposure was recommended.

1. Quesada-Cortes A, Campos-Munoz L, Diaz-Diaz RM, Casado-Jimenez M. Cold panniculitis. 

2. Bolotin D, Duffy KL, Petronic-Rosic V, Rhee CJ, Myers PJ, Stein SL. Cold panniculitis following ice therapy for cardiac arrhythmia. 

3. Bournas VG, Eilbert W. Infant with facial lesions. 

4. Markus JR, de Carvalho VO, Abagge KT, Percicotte L. Ice age: a case of cold panniculitis. 

5. Ter Poorten JC, Hebert AA, Ilkiw R. Cold panniculitis in a neonate. 

6. Polcari IC, Stein SL. Panniculitis in childhood. 

A healthy, afebrile, 12-month-old girl presents for evaluation with an asymptomatic nodule on her left cheek that has been present for 3 weeks. She was initially seen by her pediatrician, diagnosed with cellulitis, and prescribed an oral antibiotic, which was not administered by her parents.

Erythematous plaque on an infant’s cheek

A healthy 14-year-old girl with a progressive asymptomatic rash on her arms, legs, trunk, and face presents for evaluation (Figure 1). She was treated for eczema with minimal improvement.

Etiology, epidemiology, and clinical presentation

Cutaneous lymphomas are a diverse group of neoplasms that develop as an abnormal proliferation of either T- or B-lymphocytes. Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) and accounts for 54% of cases.

 In adults, hypopigmented MF (HMF) is a rare variant typically presenting in dark-skinned individuals and in those of Asian descent.

Mean age of onset is 55 to 60 years with a slight male predominance.

 Whereas CTCL is rare in the pediatric population, by some estimates representing 0.5% to 5% of total diagnoses, atypical variants predominate.

 In a review of 46 cases of MF presenting before age 16 years, 91% were ultimately diagnosed with the hypopigmented variant.

Hypopigmented MF presents with hypopigmented macules and patches. Lesions often occur on the head, neck, upper extremities, trunk, and buttocks. Erythema, scale, and papules within these macules and patches are variable. Cases have been reported in both the first and second decades of life. Histopathologically, pediatric HMF typically displays a predominantly T-suppressor CD8+ phenotype, which has a clinically benign course. This is in direct contrast to the CD4+ more clinically aggressive variant of HMF commonly diagnosed in adults.

Diffuse hypopigmentation can occur as a result of a variety of inflammatory diagnoses as well as more rare disease processes. Postinflammatory hypopigmentation is particularly common following eczematous eruptions (eg, contact and atopic dermatitis). History would include an itchy antecedent rash with improvement with therapies including daily moisturizers, topical corticosteroids, and/or calcineurin inhibitors.

Hypopigmentation is the hallmark of pityriasis alba, which manifests as minimally scaly patches on the face of children and likewise responds to eczema regimens. Pityriasis versicolor, pityriasis lichenoides chronica, and disorders of pigmentation such as progressive macular hypomelanosis and vitiligo also may be considered in appropriate clinical scenarios.

Ultimately, the diagnosis of HMF requires skin biopsy and clinicopathologic correlation. Typical histologic features of HMF include focal parakeratosis, migration of atypical T-lymphocytes into the epidermis (ie, epidermotropism), and a lymphocytic interstitial infiltrate with mild atypia of the papillary dermis. Immunohistochemical stains and T-cell gene rearrangement analyses are typically used to confirm the diagnosis.

 Histopathologic changes can require repeat skin biopsies at follow-up visits to confirm the diagnosis.

Mycosis fungoides is the most commonly diagnosed primary cutaneous lymphoma in children.

 According to the World Health Organization and the European Organization for Research and Treatment of Cancer classification system of primary cutaneous lymphomas, MF is categorized as an indolent lymphoma.

 Pediatric patients with HMF often present with limited cutaneous disease (stage IA or IB), have a good prognosis, and do not experience disease progression for years or even decades.

Because of low overall incidence and clinical presentations that mimic a variety of benign skin conditions, the diagnosis of pediatric HMF is often delayed. Furthermore, there may be reluctance among physicians to perform skin biopsies on young patients.

 Prompt diagnosis requires an adequate level of clinical suspicion, particularly for those patients with darker skin tones presenting with unusual or progressive hypopigmented lesions, with or without pruritus, that are resistant to standard therapies. Clinical evaluation should then include a lesional skin biopsy.

The most successful treatment modality across multiple series of pediatric patients with HMF has been ultraviolet light therapy, either with narrow band ultraviolet B (nbUVB) or UVA with or without psoralen photosensitization. The nbUVB therapy results in clearance within 2 to 3 years in a majority of patients.

 Other management options include observation, topical corticosteroids, and topical calcineurin inhibitors.

The patient’s skin biopsy showed a prominent atypical intraepidermal lymphoid infiltrate that was primarily CD8+ on immunohistochemistry stains (Figure 2). Her T-cell gene rearrangement studies were positive for beta and gamma gene rearrangements. Taken together, the clinical presentation and pathology results were diagnostic of CD8+ HMF and nbUVB therapy was recommended. However, the patient lived at a distance and was lost to follow-up.

1. Willemze R. Cutaneous T-cell lymphoma. In: Bolognia JL, Jorizzo JL, Rapini RP, et al. 

. 2nd ed. London: Mosby Elsevier, 2008:1867.

2. Gameiro A, Gouveia M, Tellechea Ã, Morena A. Childhood hypopigmented mycosis fungoides: a commonly delayed diagnosis. 

3. Reiter O, Ben Amitai D, Amitay-Laish I, Israeli M, Pavlovsky L, Hodak E. Pediatric mycosis fungoides: a study of the human leukocyte antigen system among Israeli Jewish patients. 

4. Heng YK, Koh MJ, Giam YC, Tang MB, Chong WS, Tan SH. Pediatric mycosis fungoides in Singapore: a series of 46 children. 

5. Patraquim C, Gomes MM, Garcez C, et al. Childhood hypopigmented mycosis fungoides: a rare diagnosis. 

6. Diwan H, Ivan D. CD8-positive mycosis fungoides and primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma. 

7. Whittam LR, Calonje E, Orchard G, Fraser-Andrews EA, Woolford A, Russell-Jones R. CD8-positive juvenile onset mycosis fungoides: an immunohistochemical and genotypic analysis of six cases. 

8. Virmani P, Levin L, Myskowski PL, et al. Clinical outcome and prognosis of young patients with mycosis fungoides. 

9. Cervini AB, Torres-Huamani AN, Sanchez-La-Rosa C, et al. Mycosis fungoides: experience in a pediatric hospital [article in English, Spanish]. 

10. Furlan FC, Sanches JA. Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology. 

11. El-Shabrawi-Caelen L, Cerroni L, Medeiros LJ, McCalmont TH. Hypopigmented mycosis fungoides: frequent expression of a CD8+ T-cell phenotype. 

12. Song SX, Willemze R, Swerdlow SH, Kinney MC, Said JW. Mycosis fungoides: report of the 2011 Society for Hematopathology/European Association for Haematopathology workshop. 

13. Laws PM, Shear NH, Pope E. Childhood mycosis fungoides: experience of 28 patients and response to phototherapy. 

14. Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002. 

A healthy 14-year-old girl with a progressive asymptomatic rash on her arms, legs, trunk, and face presents for evaluation. She was treated for eczema with minimal improvement.

Hypopigmented lesions in a teenaged girl

	Following an uncomplicated pregnancy, labor, and delivery, a healthy 13-day-old girl presents for evaluation with a 2-day history of firm, violaceous nodules on her mid-upper back and right arm just above the axilla (Figure 1).

	Subcutaneous fat necrosis of the newborn (SCFN) is an uncommon, benign disorder characterized by inflammation and necrosis of the subcutaneous fat tissue that typically presents in the first weeks of life in full-term and postterm infants.

 The etiology of SCFN is unknown but is thought to be linked to multiple neonatal and maternal risk factors including, but not limited to, perinatal hypoxia, meconium aspiration, therapeutic hypothermia, gestational diabetes, preeclampsia, maternal smoking, thrombosis, and dyslipidemia. Complications of SCFN include hypoglycemia, thrombocytopenia, hypertriglyceridemia, with the most critical being hypercalcemia.

More: Rapidly growing nodule on infant's posterior thigh

	Patients with hypercalcemia typically present with lethargy, hypotonia, irritability, vomiting, polyuria, polydipsia, constipation, and dehydration; however, some may be asymptomatic.

 There is debate about the underlying etiology of the development of hypercalcemia in neonates with SCFN. One proposed mechanism suggests increased activity of 1-alpha-hydroxylase on 25-hydroxyvitamin D by activated macrophages within the subcutaneous granulomas leads to excess intestinal calcium absorption.

 Another theory postulates that increased levels of inflammatory mediators, such as prostaglandin E, lead to activation of osteoclasts that release calcium from necrotic fat cells. At any rate, it is important to screen neonates with SCFN for hypercalcemia because, if severe and left untreated, it may lead to acute and chronic life-threatening effects on the cardiovascular and renal systems.

	With SCFN, painful, indurated, erythematous-violaceous nodules or plaques present on the arms, shoulders, back, and less commonly on the face, legs, and buttocks, in the first weeks of life.

 It is categorized as a localized form of lobular panniculitis.

 The differential diagnosis of lobular panniculitides is narrow in this age group, including sclerema neonatorum, traumatic panniculitis (eg, forceps delivery), and poststeroid panniculitis in addition to SCFN. Distinguishing SCFN and sclerema neonatorum is based on histopathologic review and clinical history. Needle-shaped crystals in a radial arrangement are a characteristic histologic feature present in both conditions (Figure 3).

	The 2 conditions are distinguished by an absence of an inflammatory infiltrate in sclerema neonatorum that is normally present in SCFN.

 Sclerema neonatorum usually presents as diffuse hardening of the skin in severely ill, hypoxic, septic, and premature infants. Poststeroid panniculitis occurs typically in children on high-dose systemic steroids whose doses were rapidly decreased or steroid therapy abruptly stopped. The cutaneous findings appear roughly 1 to 10 days after cessation of the high-dose systemic steroids and typically manifest on the cheeks because this area is where the most accumulation of fat is induced by steroids. Additionally, SCFN can be distinguished from poststeroid panniculitis based on the clinical history; however, a biopsy may still be used to differentiate the 2 diagnoses if necessary.

	Subcutaneous fat necrosis of the newborn is generally a benign, self-limiting disorder that resolves in a period of weeks to months. The management strategy includes monitoring metabolic derangements, specifically, frequent monitoring of calcium levels.

 Subtle chronic hyperglycemia may persist for 4 to 6 months. Treatment of severe hypercalcemia generally includes intravenous isotonic fluids, loop diuretics, and corticosteroids. Di Bari and colleagues implemented zoledronic acid, a bisphosphonate, in a patient who was refractory to standard treatments.

 However, most patients without severe hypercalcemia improve without treatment.

	The patient’s initial chemistry profile demonstrated a mildly elevated calcium of 10.9 mg/dL (normal range, 8.7-10.4 mg/dL). Dermatology was consulted. A punch biopsy showed necrotic adipocytes containing needle-shaped crystals in a radial arrangement typical of subcutaneous fat necrosis (Figure 2).

Next: Newborn's rash is more than skin deep

	The patient’s mother and grandmother were educated regarding her condition and reassured that her lesions would improve over weeks to months. At her 2-week follow-up, her calcium level was stable at 10.8 mg/dL and her lesions were noted to be smaller. At the 4-month follow-up, the patient’s lesions were barely palpable.

	1. Rubin G, Spagnut G, Morandi F, Valerio E, Cutrone M. Subcutaneous fat necrosis of the newborn. 

	2. Canpolat N, Özdil M, KuruÄoÄlu S, ÇalÄ±Åkan S, Sever L. Nephrocalcinosis as a complication of subcutaneous fat necrosis of the newborn. 

	3. Shumer DE, Thaker V, Taylor GA, Wassner AJ. Severe hypercalcaemia due to subcutaneous fat necrosis: presentation, management and complications. 

	4. Del Pozzo-Magaña BR, Ho N. Subcutaneous fat necrosis of the newborn: a 20-year retrospective study. 

	5. Coondoo A, Lahiry R, Choudhury A, Sengupta S. Tender skin nodules in a newborn. 

	6. Requena L, Sánchez Yus E. Panniculitis. Part II. Mostly lobular panniculitis. 

	7. Di Bari JA, Nead JA, Schurman SJ. Zoledronic acid for neonatal subcutaneous fat necrosis. 

	Mrs. Ward is a fourth-year medical student at the Medical College of Georgia, Augusta University, Augusta, Georgia. Dr Cleary is a third-year Dermatology resident, Division of Dermatology, Medical College of Georgia, Augusta University, Augusta. Dr Davis is professor and chief of Dermatology and Residency Program director for the Division of Dermatology, Medical College of Georgia, August University, Augusta. Dr. Cohen, section editor for Dermcase, is professor of Pediatrics and Dermatology at Johns Hopkins University School of Medicine, Baltimore, Maryland. The authors and section editor have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have interest in any part of this article. Vignettes are based on real cases that have been modified to allow the authors and editor to focus on key teaching points. Images also may be edited or substituted for teaching purposes.

Following an uncomplicated pregnancy, labor, and delivery, a healthy 13-day-old girl presents for evaluation with a 2-day history of firm, violaceous nodules on her mid-upper back and right arm just above the axilla.

Author | Loretta S Davis, MD

Articles

Teenager bothered by painful bumps on toes

Erythematous plaque on an infant’s cheek

Hypopigmented lesions in a teenaged girl

New violaceous nodules in a neonate