A very important symptom which sometimes occurs in this stage is a cutaneous efflorescence, which may resemble urticaria, scarlet fever, or measles. This latter resemblance is very close and often leads to diagnostic error. The efflorescence occurs most frequently in the young, and also in vaccinated adults. In some epidemics it is not at all uncommon, but as a rule it is rare.

The duration of the stage of invasion varies from two to four days. Usually it is about three days.

Period of Eruption.—Late on the third day or early on the fourth the eruption makes its appearance, and the constitutional symptoms subside to a certain extent.

The rash appears first on the confined and moist portions of the skin or in irritated parts,—under a blister, for instance, which may have been applied for the backache. Normally, it is first seen upon the forehead at the hair-line, then behind the ears and down the tender part of the neck. It gradually extends down the trunk and arms, the hands and lower extremities being affected last. The eruption generally takes from twenty-four to thirty-six hours to cover the entire body. The best location to observe the rash for diagnostic purposes is on the back, where it cannot be obscured by scratching and where the warmth of the body causes the mildest congestion to appear at its best. The exposed parts are usually ill adapted for study of the rash, being obscured by the swelling and congestion of the face and by more or less dirt or staining of the hands.

The rash consists first of small round or oval, rose-colored macules, which seem to be in the skin, coming up from beneath it, as it were. They disappear readily on pressure or on tension of the skin. When coalescence occurs, the lesions may resemble the blotches of measles. The macule at this stage is about from one-eighth to one-fourth of an inch in diameter, and its color is of an intense red which shows well at night, even by the light of a match. In less than twenty-four hours the centre of the macule becomes hard; and as this hardness increases, the lesion gradually rises above the skin. It is now changing into the papular stage. The macular stage lasts usually from eight to twenty-four hours.

The papules continue to increase slowly in size, the apex becoming flattened or indented in some lesions. While this change is going on the redness of the macule forms an areola about the hard portion or central papule. This areola tends to get smaller as the papule gets larger, and at last is completely lost.

If the pulp of the finger is passed over the papule, especially in its early stage, the latter seems to roll beneath it, giving the sensation of a small shot buried in the skin. When the papule is fully developed, the surrounding skin is put on the stretch, and the rolling sensation is lost, but the papule is so dense and hard that it is frequently described as “shotty.” The papule of varicella and of acne is not so dense and resisting as the papule of variola. The fully-developed papule in smallpox is rarely surrounded by a halo of congestion as it is in varicella, but in the modified form of smallpox this is not infrequently the case. The papule always arises from the centre of its halo like a bull’s eye, whereas in chicken-pox it arises from within the circumference, but not always in the centre. The halo of congestion in chicken-pox is always very broad and extensive, and is best seen upon the back. When a halo is present in smallpox it is very narrow and insignificant. The papule is usually fully developed in twenty-four hours.

At the end of another twenty-four or thirty-six hours the apex of the papule shows a further change. It appears to be transformed from a solid to a fluid. The color also changes as the fluid increases, and the lesion appears bluish or purplish. The fluid continues to increase in amount until the papule is converted into a little blister or vesicle. As the change is going on, the height of the papule grows less and less, and when vesiculation is complete we have a broad, flat, umbilicated vesicle with a firm, dense base. To the touch these vesicles are firm and resisting, and the membranous covering is not easily broken, unless macerated by the perspiration due to heavy flannels.

The vesicle is divided irregularly by little bands, or septa, which permit only a portion of the fluid to escape when one is punctured. Vesiculation is usually complete about the third day, and the stage generally lasts three days. It may be stated here that the reckoning in smallpox is usually from the appearance of the rash. The period of incubation and invasion are considered in reckoning the length of illness, but in descriptions of smallpox it is considered best to state the day of the eruption, and not of the disease.

There is an old and oft-repeated statement that a uniform rash is a characteristic of smallpox and that a mixed rash indicates chicken-pox. This deserves to be promptly refuted. It is most unusual to find a case of smallpox with its eruption all in one stage. While it is a well known fact that chicken-pox runs a hasty course,—so that in from one to two days we may have macules, papules, vesicles, and even crusts,—in smallpox this is not likely to occur, as the disease never runs such a rapid course. In the early stage we may see macules changing into papules on the head and the neck, while there are simply macules on the trunk. Later in the disease the eruption may be vesicular on the head while still papular on the body. When vesiculation is complete, we have the distinct umbilicated appearance that has long been recognized as a characteristic of smallpox. The vesicles are broad, firm, flat, and hard, and are invariably indented or umbilicated.